Laboratory of Molecular Cardiology
Laboratory of Molecular Cardiology
Head of the Laboratory
Prof. habil. dr. Vaiva Lesauskaitė
Phone: +370 37 302874
The laboratory was established in 2008. Prof. habil. dr. Vaiva Lesauskaitė was elected as the head of the laboratory.
1. Cardiovascular diseases genetic epidemiology.
2. Candidate genes and their variants relevant to cardiovascular morphogenesis researches.
3. Cardiovascular diseases pharmacogenetic researches.
The laboratory is involved in the clinical and research collaboration with LUHS Cardiothoracic and Vascular Surgery, Cardiology and other institutions.
Laboratory of Molecular Cardiology operating principles:
- Research must be carried on time, high-quality and in compliance with the highest EU standards.
- Laboratory workers constantly renew their knowledge of raising qualification.
- Results of scientific research results should be published in Lithuanian and international scientific journals also presented at conferences.
- Laboratory workers must carry out academic activities, sharing of experience and knowledge.
- Mission – increase the diagnostic molecular genetics research availability for Lithuanian residents.
- Vision – health care quality improvement. Physicians using diagnostic molecular genetics research results more accurately diagnose diseases and will better predict their process and choose the most appropriate treatment strategy.
- Strategy – execution of laboratory activities are integrating clinical diagnostic and research laboratory quality system into the management system and operation of accreditation, according to standard. BS EN ISO / IEC 17025 standard.
Vaiva Lesauskaitė habil. dr. , chief researcher / head of the laboratory
Giedrė Jarienė dr. , researcher
Alina Smalinskienė dr. , researcher
Sandrita Šimonytė dr. , researcher
Ramunė Šepetienė dr. , junior researcher
Vacis Tatarūnas dr. , senior researcher
Audronė Veikutienė dr. , researcher
Vilius Skipskis dr. , researcher
Vaiva Patamsytė, junior researcher
Lukas Gudaitis, junior researcher
Ona Rūta Šereivienė, senior laboratory assistant
Dovydas Gečys, laboratory assistant
Edita Kuncevičienė, laboratory assistant
Ieva Eitminavičiūtė, laboratory assistant
1. Project title: National research programme “Chronic non-communicable diseases”: Pathology of ascending aorta: search for molecular and biomechanical markers of dilatation
Summary: Dilatative pathology of ascending aorta (DPAA) is a well-known life-threatening condition for aortic dissection.
DPAA usually develops without any symptoms before clinically manifested sudden aortic wall dissection. One of the most feasible methods for the diagnosis of aortic dilation is 2D echocardiography, however it is not relevant for prediction of dilation rate and prevention of complications. Therefore, noninvasive predictors of aortic dilation are required and the aim of the study was to reveal molecular, morphometric and biomechanical markers of remodeled aortic wall for prediction of aortic dilation, for early diagnosis and decision making.
Two-dimensional (2D) and 2D speckle-tracking echocardiography confirmed that the dilated aorta could not produce normal movement during several cardiac cycles, which could be a predictor of possible mechanical complications (M.Bieseviciene et al. BMC Cardiovasc Disord. 2017; 17: 27).
Our study provided further evidence that FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and FBN1 SNPs rs2118181 and rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection. The aortic dissection development in the absence of these risk alleles stresses that aortic dissection is a complex pathological process and various clinical and biological factors might impact its respective risk (V.Lesauskaitė et al. Eur J Cardiothorac Surg, 2015;47:e124-e130).
We reported a significant association between TGF-β1 concentration and DPAA but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-β1 concentration in patients with sporadic DPAA in comparison to the reference subjects requires further investigation to establish its role in sporadic DPAA pathogenesis. We would also like to raise awareness regarding the choice of methods when measuring TGF-β1 levels with an emphasis on preanalytical phase and the choice of sample (R.Sepetiene et al. PLOSone, 2015. 10(6):e0129353).
Our study for the first time demonstrated the association between TGF-β1 levels in blood plasma and FBN1 SNPs rs2118181 and rs10519177 in a random sample of population. We suggest that TGF-β1 levels in blood plasma in combination with FBN1 SNPs might serve as a biomarker to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection (R.Sepetiene et al. Mol Med; 2015,21:735-738).
Funding: Project No. LIG-05/2012 was funded by Research Council of Lithuania.
Project duration: 2012 – 2014.
2. Project title: ”Personalized clopidogrel therapy according to patient genotype“
Summary of results: The main task of this project was to determine clinically important polymorphisms of the genes CYP2C19 (*1, *2 and *3), CYP2C9 (*1,*2 and *3), ABCB1 (C3435T), fibrinogen (G-455A) and (C-148T), thrombin (C494T), which influence antiplatelet effect of clopidogrel and to assess the frequency of gene polymorphisms in a random sample of Lithuanian population.
Sequence standards were determined by using Sanger sequencing of the genes CYP2C19 (*1, *2 and *3), CYP2C9 (*1,*2 and *3), ABCB1 (C3435T), fibrinogen (G-455A) and (C-148T), thrombin (C494T). Real-Time polymerase chain reaction was used to identify polymorphism of the genes CYP2C19 (*1, *2 and *3), CYP2C9 (*1,*2 and *3), ABCB1 (C3435T), fibrinogen (G-455A) and (C-148T), thrombin (C494T) in three groups of subjects: main group, group of the patients who experienced stent thrombosis and in the random population sample. We assessed the impact of represented genotypes and their variants on platelet function during antiplatelet therapy. We also assessed the influence of clinical and genetic factors (age, diabetes, concomitant drugs) on platelet function during antiplatelet therapy. We determined the most important biomarkers, who might help to identify patients of high risk of stent thrombosis. We determined CYP2C19 (*1, *2 and *3), CYP2C9 (*1,*2 and *3), ABCB1 (C3435T), fibrinogen (G-455A) and (C-148T), thrombin (C494T) polymorphisms in the random sample and we compared the frequencies of these polymorphisms with patient samples.
We found that platelet aggregation (PA) with ADP was lower in one third of the patients who carried FI C-148C, but not in the FI T-148T genotype carriers who were treated 4 weeks after induction of treatment with aspirin and clopidogrel. CYP2C19, CYP2C9 or ABCB1 had no impact on platelet aggregation during induction or 4 weeks after induction of the treatment.
60 years and older, diabetic patients, patients having more than 90 centimeters of body waist, had higher PA values. Higher PA was observed in aspirin non-users or statin users during long-term treatment. Perindopril and zofenopril had a different effect. First one has PA lowering-effect during induction, the second one - during long-term treatment. During induction of the treatment, the use of benzodiazepines decreased PA after induction with ARA. During long-term treatment it had an opposite effect.
CYP2C19 *2*2 was 4 times and fibrinogen TT genotype was two times more prevalent in patients who had stent thrombosis than in patients without stent thrombosis. Patients with stent thrombosis, who carried FI C-148C genotype, were older. We found a tendency that younger patients, carriers of T allele had stent thrombosis more frequently.
The prevalence of CYP2C19, ABCB1 and FI C-148T genotypes was similar in a random sample and in a sample of patients without stent thrombosis. CYP2C19*2*2 genotype was 11 times and fibrinogen T-148T genotype was 1.7 times more prevalent in patients who had stent thrombosis than in a random sample.
Funding: Project No. MIP-038/2013 was funded by Research Council of Lithuania.
Project duration: 2013 – 2015.
3. Project title: ”Personalized antiplatelet therapy in patients with acute coronary symdromes: biomarkers of blood coagulation and fibrinolysis system“
Summary: Treatment of acute coronary syndromes (ACS) is not always effective. The causes are not always evident. During this project we expect to determine clinically important biomarkers, which defines antiplatelet (of clopidogrel, which is in use for about 10 years, as well as of the novel agent - ticagrelor) clinical effect in the patients who were treated for acute coronary syndromes. We believe, that the antiplatelet effect such as novel (ticagrelor), or other drugs, which are widely prescribed in clinical practice might be determined according to the activity of naturally occuring antiplatelet and other bio-active arachidonic acid metabolites which have an effect on inflammation. During this project we plan to detect 4 clinically important polymorphisms of CYP4F2, to determine enzyme activity and to investigate arachidonic acid (20-HETE) and leukotriene B4 metabolite concentrations in blood plasma. Identification of the new biomarkers might lead to proper individualization of the treatment and to improve current treatment methods for diseases, affecting the quality and healthy life.
Funding: Project No. SEN-09/2015 is funded by Research Council of Lithuania.
Project duration: 2015 – 2018.
4. Project title: National research programme “Healthy Ageing”: Age-related remodelling of aorta and dilatative pathology of ascending aorta: search for epigenetic biomarkers
Summary: The partner of the project: Institute of Biotechnology, Vilnius University (VU);
The research focuses on the hypothesis that there is an association between age related aortic wall remodelling and the formation of dilatative pathology of ascending aorta (DPAA). The prevalence of DPAA increases with age, therefore the underlying pathogenic mechanisms could be related. One of the mechanisms is post-transcriptional regulation of phenotypic changes in smooth muscle cells of aortic media. We aim to get a new insight into the aging processes and the mechanisms of age related diseases and to evaluate the potential of non-coding RNA (microRNA )to be used as biomarkers for DPAA and their diagnostic capacity to predict a clinical course of aortic remodelling.
The first part of a project was dedicated to the collection of sample material and optimization of test methods. Protocols for laboratory analyses were optimized to use MirVana Ambion kit for RNA extraction and homogenising aortic tissue sample using liquid nitrogen before cell lysis. A 0.5 ml blood plasma sample was selected for RNA extraction using MirVana Paris kit. MiRNA sequencing analysis of six aortic tissue samples and five blood plasma samples showed a statistically significant increase in 18 miRNAs and decrease in 10 miRNAs expression levels in TAA samples compared to healthy aortic tissue. In current stage the role of identified miRNA in TGF-beta signaling pathway is under investigation. Only a small fraction of the identified changes in miRNA expression are published in current literature, so there is a great possibility to discover novel biomarkers for TAA.
Practical recommendation: Intervening procedures and deviation from plasma collection protocol often cause erythrocyte breakdown during blood plasma sample collection. Our findings as well as other studies show that erythrocyte specific miRNAs are released into plasma during this degradation process. This complicates evaluation on circulating miRNA expression profiles in blood, especially miRNAs present at a very low concentration levels. During optimisation of RNA extraction method from blood plasma we have established that only in plasma samples which had absorption at a 414 nm wavelength (A414) lower than 0.2, erythrocyte haemolysis did not interfere with miRNA expression analyses. Later in the study we have noticed that this value is strongly associated with other blood characteristics (i.e. lipid concentration in blood, use of medicine) and can increase above 0.2 even if haemolysis in blood plasma is not present. Taken into consideration these factors, when evaluating haemolysis levels, it is necessary to assess expression of miRNAs associated with erythrocyte: miR-16-5p and miR-451a-5p, since their concentration is dependent on the level of haemolysis. Summing up these results we recommend to check erythrocyte haemolysis level in selected blood plasma samples before carrying out miRNA expression analysis ( miRNA sequencing, identification and validation of potential biomarkers) using the following methods: measuring plasma sample absorption (A414), checking erythrocyte associated miRNA expression levels, and analysing samples which do not have haemolysis.
Funding: Project No. SEN-05-2016 is funded by Research Council of Lithuania.
Project duration: 2016 – 2018.
5. Project title: ”Point-of-Care method for ticagrelor pharmacogenomics (OPTOGEN)“
Summary: The aim of the project is to develop a new device that will allow to individualize treatment with ticagrelor "Point-of-Care" and, during the prospective research in the patients prescribed antiplatelet drugs, to validate a new bio-marker for the treatment individualization with ticagrelor. The project will be implemented in stages.
During the first stage, a rapid genotyping method and dedicated equipment will be developed. That will allow to detect a selected bio-marker in one tube without DNA extraction. In the second stage, prospective studies will be carried out with the patients before antiplatelet therapy prescription (n = 100). During this stage, the prognostic value of the selected biomarker will be evaluated for further individualization of the treatment with ticagrelor. The research will be carried out according to the following principle: the patient`s genotype will be determined prior to the antiplatelet prescription, depending on the results of the genotyping. Thus, a patient will receive an individualized therapy depending on the genotyping results (ticagrelor or alternative drug) and the recommended dosage.
Results of the project: During the project the impact of a bio-marker involved in ticagrelor pharmacogenomics will be determined. A newly developed device will be applied for a patent in European Patent Office. The obtained scientific results (excluding the final report of the project) will be published in at least one research journal with impact factor higher than 2.
The use of the results of this project are obvious in the Lithuanian and in global scale, as these results will allow to proper dosage one of the most commonly used anti-platelet drugs, which are currently used in clinical practice and will help to prevent the undesirable effects of drug usage. Both the developed method and device would be also used in a wider circle of researchers. The results of the project will be implemented through direct contact with physicians and scientists working in the mentioned area. The results will be made available to the public through social networks.
Funding: Project No. 01.2.2-LMT-K-718-01-0038 is funded by European Regional Development Fund.
Project duration: 2017 – 2021.
6. Project title: ”Centre of Excellence in Science and Technology for Healthy Ageing (HEALTH-TECH)“
Summary: Centre of Excellence in Science and Technology for Healthy Ageing is under development by Kaunas University of Technology,LithuanianUniversityof Health Sciences, andVilniusUniversitywith support by partners of the Baltic Sea region- Teknologian Tutkimuskeskus VTT (VTT) inFinland,UniversityofLundinSweden.
In the context of ageing populations inEuropeand many other countries around the world, high impacting challenges are expected to hit societies and economies. Among them, the growing phenomenon of multi-morbidity (MM), which is the simultaneous occurrence of several non-communicable diseases (NCDs) in a patient, is a major concern. MM is still poorly addressed in medical care and treatment, since the standard approaches focus on single-disease diagnostics and treatments. Yet, MM is a major concern for patients, whose quality of life is significantly impaired, social inclusion impacted, and risk of death increased. It also critically affects the economy, through the resulting high cost of healthcare, the poverty many MM patients face, or the reduced labour participation MM causes.
The problem of MM opens a major route for research, as a better understanding is required. It also brings important innovation opportunities, since solutions for prevention, diagnostics, care and treatment of MM must be developed.
The proposal was aimed to address the problem of MM by preparing the business plan proposing the creation of a Centre of Excellence (CoE) inLithuanianamed Health-Tech.
Health-Tech’s vision is to become a leading Baltic Sea Region CoE of advance knowledge-based innovations for prediction, early diagnostics and personalised management of MM of ageing persons, with the aim to enhance their quality of life and improve the effectiveness of healthcare systems. The Health-Tech CoE will have a particular focus on collaboration with global healthy ageing research and innovation networks.
Health-Tech’s mission is 1) to provide international and interdisciplinary leadership, to create and transfer advanced knowledge, technology and integrated solutions for prediction, early diagnostics and personalised management of multi-morbidity of ageing persons; 2) to foster talents of new generation of innovation-oriented researchers and professionals; 3 to promote management of MM among ageing persons, their families and across different levels of the healthcare system.
The CoE is founded by five higher education and research partners: three fromLithuania(Kaunas University of Technology, LithuanianUniversityofHealth Sciences,VilniusUniversity), one fromSweden(LundUniversity), and one fromFinland(VTT Technical Research Centre of Finland). The five partners will, through a Joint Activity Agreement, establish the CoE according to a Long-Term Research and Innovation Strategy. The clinical focus will be four types of disease (cardio-vascular diseases (CVD); bone and joint diseases; neurodegenerative diseases (ND); and gastrointestinal dysfunction), and the research focus will be on four themes:
Genomics and proteins structures and functions for personalised management of MM patterns.
Personalised sets of multifactorial biomarkers for early diagnostics of MM patterns.
Multimodal biosignal, imaging and IT for personalised early diagnostics and monitoring of MM patterns.
Tissue engineering in age-related MM management.
Prepared business plan will applied for Horizont 2020 call.
Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 664339.
2018 – 2017
- A novel ultrasonic method for evaluation of blood clotting parameters. Vacis Tatarunas, Algirdas Voleisis, Reimondas Sliteris, Rymantas Kazys, Liudas Mazeika, Vaiva Lesauskaite. Journal of medical ultrasonics. Tokyo: Springer Japan. (Original article). ISSN 1346-4523. 2018, vol. 00, no. 00, p. 00-00. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; 0.471. Internet access
- MMP-2 Rs24386 (C-->T) gene polymorphism and the phenotype of age-related macular degeneration. Rasa Liutkeviciene, Vaiva Lesauskaite, Giedre Sinkunaite-Marsalkiene, Sandrita Simonyte, Reda Zemaitiene, Loresa Kriauciuniene, Dalia Zaliuniene. International journal of ophthalmology. Xi'an, China: Press of International Journal of Ophthalmology (IJO PRESS). (Basic research). ISSN 2222-3959. 2017, vol. 10, no. 9, p. 1349-1383. Science Citation Index Expanded (Web of Science); MEDLINE; DOAJ; 0.495. Internet access
- Traditional risk factors of acute coronary syndrome in four different male populations – total cholesterol value does not seem to be relevant risk factor. J. A. Hubacek, V. Stanek, M. Gebauerova, V. Adamkova, V. Lesauskaite, D. Zaliaduonyte-Peksiene, A. Tamosiunas, A. Supiyev, A. Kossumov, A. Zhumadilova, J. Pitha. Physiological research. Prague: Institute of Physiology of the Czech Academy of Sciences. ISSN 0862-8408. 2017, vol. 66, suppl. 1, p. S121-S128. Science Citation Index Expanded (Web of Science); 0.445. Internet access
- SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area. Daiva Stanislovaitiene, Dalia Zaliuniene, Algimantas Krisciukaitis, Robertas Petrolis, Alina Smalinskiene, Vita Lesauskaite, Abdonas Tamosiunas, Vaiva Lesauskaite. Ophthalmic genetics. London: Informa Healthcare. ISSN 1381-6810. 2017, vol. 38, no. 3, p. 233-237. Science Citation Index Expanded (Web of Science); MEDLINE; 0.65. Internet access
- Prevalence of O25b-ST131 clone among Escherichia coli strains producing CTX-M-15, CTXM- 14 and CTX-M-92 β-lactamases. Agnė Giedraitienė, Astra Vitkauskienė, Alvydas Pavilonis, Vaiva Patamsytė, Nathalie Genel, Dominique Decre, Guillaume Arlet. Infectious diseases. Abingdon, England: Taylor & Fransis Ltd. (Original article). ISSN 2374-4235. 2017, vol. 49, no. 2, p. 106-112. Science Citation Index Expanded (Web of Science); MEDLINE; Index Veterinarius; 0.35. Internet access
- Two-dimensional speckle-tracking echocardiography for evaluation of dilative ascending aorta biomechanics. Monika Bieseviciene, Jolanta Justina Vaskelyte, Vaida Mizariene, Rasa Karaliute, Vaiva Lesauskaite, Raimonda Verseckaite. BMC cardiovascular disorders. London: BioMed Central. (Research article). ISSN 1471-2261. 2017, vol. 17, no. 1, p. 1-11. Science Citation Index Expanded (Web of Science); MEDLINE; 0.471. Internet access
- The Impact of clinical and genetic factors on ticagrelor and clopidogrel antiplatelet therapy. Vacis Tatarunas, Nora Kupstyte, Remigijus Zaliunas, Agne Giedraitiene, Vaiva Lesauskaite. Pharmacogenomics. London: Future Medicine. (Research article). ISSN 1462-2416. 2017, vol. 18, no. 10, p. 969-979. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; 0.693. Internet access
- The Impact of CYP2C19*2, CYP4F2*3, and clinical factors on platelet aggregation, CYP4F2 enzyme activity, and 20-hydroxyeicosatetraenoic acid concentration in patients treated with dual antiplatelet therapy. Vacis Tatarunas, Nora Kupstyte, Agne Giedraitiene, Vilius Skipskis, Valdas Jakstas, Vaidotas Zvikas, Vaiva Lesauskaite. Blood coagulation & fibrinolysis. London: Lippincott, Williams & Wilkins. (Original article). ISSN 0957-5235. 2017, vol. 28, no. 8, p. 658-664. Science Citation Index Expanded (Web of Science); MEDLINE; 0.742. Internet access
- Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents. Sandrita Simonyte, Renata Kuciene, Jurate Medzioniene, Virginija Dulskiene, Vaiva Lesauskaite. BMC medical genetics. London: BioMed Central. (Research article). ISSN 1471-2350. 2017, vol. 18, no. 1, p. 1-9. Science Citation Index Expanded (Web of Science); MEDLINE; DOAJ; Scopus; 1. Internet access
- Association of the genetic and traditional risk factors of ischaemic heart disease with STEMI and NSTEMI development. Diana Žaliaduonytė-Pekšienė, Vaiva Lesauskaitė, Rasa Liutkevičienė, Vytenis Tamakauskas, Vilius Kviesulaitis, Giedrė Šinkūnaitė-Maršalkienė, Sandrita Šimonytė, Simonita Mačiulskytė, Eglė Tamulevičiūtė-Prascienė, Olivija Gustienė, Abdonas Tamošiūnas, Remigijus Žaliūnas. Journal of the renin-angiotensin-aldosterone system. London: Sage. (Original article). ISSN 1470-3203. 2017, vol. 18, no. 4, p. 1-9. Science Citation Index Expanded (Web of Science); MEDLINE; DOAJ; 0.433. Internet access
- MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing. Ugne Gyvyte, Simonas Juzenas, Violeta Salteniene, Juozas Kupcinskas, Lina Poskiene, Laimutis Kucinskas, Sonata Jarmalaite, Kristina Stuopelyte, Ruta Steponaitiene, Georg Hemmrich-Stanisak, Matthias Hübenthal, Alexander Link, Sabine Franke, Andre Franke, Dalia Pangonyte, Vaiva Lesauskaite, Limas Kupcinskas, Jurgita Skieceviciene. Oncotarget. Albany, N.Y.: Impact Journals. ISSN 1949-2553. 2017, vol. 8 no. 23, p. 37225-37238. [Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; 0.351. Internet access
- The Effect of sodium valproate on the glioblastoma U87 cell line tumor development on the chicken embryo chorioallantoic membrane and on EZH2 and P53 expression. Dovilė Kavaliauskaitė, Donatas Stakišaitis, Justė Martinkutė, Lina Šlekienė, Arūnas Kazlauskas, Ingrida Balnytė, Vaiva Lesauskaitė, Angelija Valančiūtė. BioMed research international. New York: Hindawi Publishing Corporation. (Research article). ISSN 2314-6133. 2017, vol. 2017, p. 1-12. Science Citation Index Expanded (Web of Science); MEDLINE; DOAJ; Scopus; 0.25. Internet access
- Investigation of TGFβR2 SNP rs4522809, Osteopontin, TGF β1 and their association with dilatative pathology of ascending thoracic aorta. Zivile Staneviciute, Ramune Sepetiene, Ingrida Grabauskyte, Vaiva Patamsyte, Vaiva Lesauskaite. Cytokine. Oxford: Elsevier. ISSN 1043-4666. 2017, vol. 00, no. 00, p. 00-00. Science Citation Index Expanded (Web of Science); MEDLINE; 0.8. Internet access
- Physical activity, but not dietary intake, attenuates the effect of the FTO rs9939609 polymorphism on obesity and metabolic syndrome in Lithuanian adult population. J. Petkeviciene, A. Smalinskiene, J. Klumbiene, V. Petkevicius, V. Kriaucioniene, V. Lesauskaite. Public health. Amsterdam: Elsevier. (Original research). ISSN 0033-3506. 2016, vol. 135, p. 23-29. Science Citation Index Expanded (Web of Science); MEDLINE; BIOSIS; Excerpta Medica; Scopus; 0.471. Internet access
- Multiplicity of effects and health benefits of resveratrol. Lolita Kuršvietienė, Inga Stanevičienė, Aušra Mongirdienė, Jurga Bernatonienė. Medicina. Wrocław: Elsevier. (Reviews). ISSN 1010-660X. 2016, vol. 52, no. 3, p. 148-155. Science Citation Index Expanded (Web of Science); MEDLINE; IndexCopernicus; Scopus; 0.433. Internet access
- Role of MMP-2 (-1306 C/T) polymorphism in age- related macular degeneration. Rasa Liutkeviciene, Vaiva Lesauskaite, Diana Zaliaduonyte-Peksiene, Giedre Sinkunaite-Marsalkiene, Dalia Zaliuniene, Vaida Mizariene, Olivija Gustiene, Vytautas Jasinskas, Abdonas Tamosiunas. Ophthalmic genetics. London: Informa Healthcare. (Research report). ISSN 1381-6810. 2016, vol. 37, no. 2, p. 170-176. Science Citation Index Expanded (Web of Science); MEDLINE; 0.385. Internet access
- Gene polymorphism of CYP2C19*2, *3 and CYP3A4*1B and early stent thrombosis: case reports and literature review. Nazgul Kulmyrzaeva, Vacis Tatarunas, Vilius Skipskis, Gaziza Smagulova, Nazgul Seitmaganbetova, Audrone Veikutiene, Vaiva Lesauskaite. Personalized medicine. London: Future Medicine. (Case series). ISSN 1741-0541. 2016, vol. 13, no. 5, p. 423-428. Science Citation Index Expanded ( Web of Science); 0.808. Internet access
- Characteristics of expression of matrix metalloproteinases (MMP-2 and MMP-9) in glottic squamous cell carcinoma and benign vocal fold lesions. Uloza V, Liutkevicius V, Pangonyte D, Lesauskaite V. Clinical and experimental otorhinolaryngology. Seoul: Korean Society of Otorhinolaryngology-Head and Neck Surgery. (Original article). ISSN 1976-8710. 2015, vol. 8, no. 1, p. 57-64. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; Synapse; 0.707. Internet access
- Effect of physical training on indices of platelet aggregation and fibrinogen concentration in patients with chronic heart failure. Aušra Mongirdienė, Raimondas Kubilius. Medicina. Wrocław: Elsevier. (Original research article). ISSN 1010-660X. 2015, vol. 51, no. 6, p. 343-350. Science Citation Index Expanded (Web of Science); MEDLINE; IndexCopernicus; Scopus; 0.707. Internet access
- The Role of matrix metalloproteinases polymorphisms in age-related macular degeneration. Liutkeviciene R, Lesauskaite V, Sinkunaite-Marsalkiene G, Zaliuniene D, Zaliaduonyte-Peksiene D, Mizariene V, Gustiene O, Jasinskas V, Jariene G, Tamosiunas A. Ophthalmic genetics. London: Informa Healthcare. ISSN 1381-6810. 2015, vol. 36, no. 2, p. 149-155. Science Citation Index Expanded (Web of Science); MEDLINE; 0.52. Internet access
- Exogenous connexin43-expressing autologous skeletal myoblasts ameliorate mechanical function and electrical activity of the rabbit heart after experimental infarction. Antanavičiūtė I, Ereminienė E, Vysockas V, Račkauskas M, Skipskis V, Rysevaitė K, Treinys R, Benetis R, Jurevičius J, Skeberdis VA. International journal of experimental pathology. Oxford, OX: Blackwell Scientific Publications. (Original article). ISSN 0959-9673. 2015, vol. 96, no. 1, p. 42-53. Science Citation Index Expanded (Web of Science); MEDLINE; Index Veterinarius; CAB Abstracts® (CABI); 1.342. Internet access
- FBN1 polymorphisms in patients with the dilatative pathology of the ascending thoracic aorta. Lesauskaite V, Sepetiene R, Jariene G, Patamsyte V, Zukovas G, Grabauskyte I, Stanioniene Z, Sirmenis R, Benetis R. European journal of cardio-thoracic surgery. Kidlington, Oxford, UK: Elsevier Science. ISSN 1010-7940. 2015, vol. 47, no. 4, p. e124-e130. Science Citation Index Expanded (Web of Science); MEDLINE; 1.556. Internet access
- Effect of clinical factors and gene polymorphism of CYP2C19*2, *17 and CYP4F2*3 on early stent thrombosis. Kupstyte N, Zaliunas R, Tatarunas V, Skipskis V, Zaliaduonyte-Peksiene D, Grabauskyte I, Dovidaitiene D, Bumblauskas K, Gustiene O, Lesauskaite V. Pharmacogenomics. London: Future Medicine. (Research article). ISSN 1462-2416. 2015, vol. 16, no. 3, p. 181-189. cience Citation Index Expanded (Web of Science); MEDLINE; Biological Abstracts; BIOSIS Previews; Prous Science Integrity®; Scopus; 0.693. Internet access
- Blood plasma TGF- β1 concentration in sporadic dilatative pathology of ascending aorta: more questions than answers. Sepetiene R, Patamsyte V, Zukovas G, Jariene G, Stanioniene Z, Benetis R, Lesauskaite V. PloS One. San Francisco: Public Library of Science. (Research article). ISSN 1932-6203. 2015, vol. 10, no. 6, p. 1-7. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; DOAJ; Chemical Abstracts Service (CAS); AGRICOLA; PyscINFO; Zoological Records; FSTA (Food Science and Technology Abstracts); GeoRef; 1.485. Internet access
- The Effect of PAI-1 4G/5G polymorphism and clinical factors on coronary artery occlusion in myocardial infarction. Parpugga TK, Tatarunas V, Skipskis V, Kupstyte N, Zaliaduonyte-Peksiene D, Lesauskaite V. Disease markers. New York: Hindawi Publishing Corporation. (Research article). ISSN 0278-0240. 2015, vol. 2015, p. 1-8. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; 0.866. Internet access
- Association between fibrillin1 polymorphisms (rs2118181, rs10519177) and transforming growth factor β1 concentration in human plasma. Ramune Sepetiene, Vaiva Patamsyte, Giedrius Zukovas, Giedre Jariene, Zita Stanioniene, Rimantas Benetis, Abdonas Tamosiunas, Vaiva Lesauskaite. Molecular medicine. Manhasset, NY: Feinstein Institute for Medical Research. ISSN 1076-1551. 2015, vol. 21, p. 735-738. Science Citation Index Expanded (Web of Science); MEDLINE; 1.516. Internet access
- Local and systemic immune responses in gingivitis and periodontitis. Gediminas Zekonis, Ingrida Barzdziukaite, Jonas Zekonis, Renata Sadzeviciene, Sandrita Simonyte, Juozas Zilinskas. Central European Journal of Medicine. Berlin: Springer. (Research article). ISSN 1895-1058. 2014, vol. 9, iss. 5, p. 694-703. Science Citation Index Expanded (Web of Science); Global Health; IndexCopernicus; Scopus; 0.289. Internet access
- The Effect of CYP2C9, VKORC1 and CYP4F2 polymorphism and of clinical factors on warfarin dosage during initiation and long-term treatment after heart valve surgery. Tatarunas V, Lesauskaite V, Veikutiene A, Grybauskas P, Jakuska P, Jankauskiene L, Bartuseviciute R, Benetis R. Journal of thrombosis and thrombolysis. [Dordrecht ; Norwell, MA]: Kluwer Academic Publishers. ISSN 0929-5305. 2014, vol. 37, no. 2, p. 177-185. Science Citation Index Expanded (Web of Science); MEDLINE; 0.707. Internet access
- Left ventricular remodelling after acute myocardial infarction: Impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene. Zaliaduonyte-Peksiene D, Simonyte S, Lesauskaite V, Vaskelyte J, Gustiene O, Mizariene V, Jurkevicius R, Jariene G, Tamosiunas A, Zaliunas R. Journal of the renin-angiotensin-aldosterone system : JRAAS. London: SAGE Publications. ISSN 1470-3203. 2014, vol. 15, no. 3, p. 286-293. Science Citation Index Expanded (Web of Science); MEDLINE; 0.866. Internet access
- The Role of clinical parameters and of CYP2C19 G681 and CYP4F2 G1347A polymorphisms on platelet reactivity during dual antiplatelet therapy. Tatarunas V, Jankauskiene L, Kupstyte N, Skipskis V, Gustiene O, Grybauskas P, Lesauskaite V. Blood coagulation & fibrinolysis. London: Lippincott Williams And Wilkins. ISSN 0957-5235. 2014, vol. 25, no. 4, p. 369-374. Science Citation Index Expanded (Web of Science); MEDLINE; 0.742. Internet access
- Effect of Acanthopanax senticosus on the accumulation of cadmium and on the immune response of spleen cells. Smalinskiene A, Savickiene N, Zitkevicius V, Pangonyte D, Sadauskiene I, Kasauskas A, Ivanov L, Lesauskaite V, Savickas A, Rodovičius H. Journal of toxicology and environmental health. Part A. Philadelphia: Taylor & Francis. ISSN 1528-7394. 2014, vol. 77, no. 21, p. 1311-1318. Science Citation Index Expanded (Web of Science); MEDLINE; CAB Abstracts; 0.52. Internet access
- Physical, behavioural and genetic predictors of adult hypertension: the findings of the Kaunas cardiovascular risk cohort study. Petkeviciene J, Klumbiene J, Simonyte S, Ceponiene I, Jureniene K, Kriaucioniene V, Raskiliene A, Smalinskiene A, Lesauskaite V. PLoS One. San Francisco: Public Library of Science. ISSN 1932-6203. 2014, vol. 9, no. 10, p. 1-9. Science Citation Index Expanded (Web of Science); MEDLINE; Scopus; Chemical Abstracts Service (CAS); PyscINFO; Zoological Records; FSTA (Food Science and Technology Abstracts); GeoRef; DOAJ; 0.577. Internet access
- The Effect of Polyscias filicifolia Bailey biomass tincture on the protein synthesis process in the heterogeneous system from the isolated pig heart. Artūras Kašauskas, Aušra Mongirdienė. Medicina. Kaunas: Lietuvos sveikatos mokslų universitetas. (Experimental investigation). ISSN 1010-660X. 2013, t. 49, Nr. 6, p. 278-283. Science Citation Index Expanded (Web of Science); MEDLINE; IndexCopernicus; Scopus; 0.707. Internet access
- SCARB1 single nucleotide polymorphism (rs5888) is associated with serum lipid profile and myocardial infarction in an age- and gender-dependent manner. Stanislovaitiene D, Lesauskaite V, Zaliuniene D, Smalinskiene A, Gustiene O, Zaliaduonyte-Peksiene D, Tamosiunas A, Luksiene D, Petkeviciene J, Zaliunas R. Lipids in health and disease. [London]: BioMed Central. ISSN 1476-511X. 2013, vol. 12, p. 1-8. Science Citation Index Expanded (Web of Science); MEDLINE; CABI; Food Science and Technology Abstracts; Scopus; 0.693. Internet access
- Association between APOE, SCARB1, PPAR alpha polymorphisms and serum lipids in a population of Lithuanian adults. Smalinskiene A, Petkeviciene J, Luksiene D, Jureniene K, Klumbiene J, Lesauskaite V. Lipids in health and disease. [London]: BioMed Central. ISSN 1476-511X. 2013, vol. 12, p. 1-8. Science Citation Index Expanded (Web of Science); MEDLINE; CABI; CAS; Food Science and Technology Abstracts; Scopus; 0.943. Internet access
- Polyacrylamide gels with ionized functional groups in their selective recognition of trimeric molecular form of human growth hormone. Rimantas Kublickas, Giedrė Jarienė. Polymer bulletin. New Yor: Springer. (Original paper). ISSN 0170-0839. 2013, vol. 70, no. 3, p. 985-992. [Science Citation Index Expanded (Web of Science); Scopus; Materials Science Citation Index; VINITI - Russian Academy of Science; 0.866. Internet access
The Research Group supervised by Prof. habil. dr. Feliksas F. Bukauskas was established in April 2015 and was incorporated into the Laboratory of Molecular Cardiology. Professor Feliksas Bukauskas was awarded by association „Global Lithuanian Leaders“ for „implementation of international innovations in Lithuania“ in December 2016. Nomination video Article
Professor habil. dr. Feliksas Bukauskas and the President of Lithuania Dalia Grybauskaitė during the event „Global Lithuanian Awards“. Photographer – Martynas Zaremba.
Research topics of the research group:
The properties and functional role of gap junction channels, formed of connexin protein, in shaping behaviour of cardiovascular and neural circuits under normal and pathological conditions:
- Structure-function studies of connexin-based channels.
- Voltage and chemical gating of gap junction channels.
- Modeling and experimental studies of cardiac and neuronal networks.
Vytautas Kazimieras Verselis prof. dr. , chief researcher
Lina Rimkutė dr. , senior researcher
Tadas Kraujalis dr. , researcher
Mindaugas Šnipas dr. , senior researcher
Kęstutis Maciūnas, junior researcher / PhD student
Lukas Gudaitis, PhD student
1. Project title: “Structure-function studies of pH sensitivity of gap junction channels”
Project objective: structure-function studies of gap junction (GJ) channels sensitivity to intracellular pHi and expanding a gating model of GJ channels by including a dependence not only on Vj but also on pHi.
The major goal - structure-function studies of gap junction (GJ) channels sensitivity to acidosis. GJs are formed of connexin (Cx) protein and are responsible for electrical and metabolic cell-cell communication. Experiments will be performed in coupling-deficient RIN cells transfected with Cx36 and Cx43. Junctional conductance (gj) under normal and variety of experimental conditions will be measured in cell pairs using a dual whole-cell voltage clamp. Our reported and preliminary data show that acidification increases the open channel probability of Cx36 GJs expressed by neurons and pancreatic ß-cells what determines their resistance to intracellular pH (pHi) decay to ~6 during ischemia. On the contrary, Cx43 GJs expressed in astrocytes and cardiomyocytes, are fully blocked at pHi=~6. We have shown that GJs contain 'fast' and 'slow' gates, which determine modulation of GJs depending on transjunctional voltage (Vj), pHi and others factors. Our data show that differences in sensitivity among Cx36 and Cx43 GJs to pHi are defined by differences in the sequence of amino acid (AA) in the N-terminus (NT) of Cxs. To determine Cx domains that are responsible for sensitivity to pH, we will study mutants in which AAs will be replaced among Cx36 and Cx43 individually or in groups. By measuring gj and its steady-state dependence of on Vj at different pHi, we will examine influence of pHi on fast and slow gates. This will allow us to detail domains in the NT region that are responsible for differences in sensitivity to pHi among Cx36 and Cx43. The data will be analysed using a gating model of GJ channels (GMGJC). In doing so, we will expand our reported GMGJC including a dependence not only on Vj but also on pHi. A principal concept of this model and its viability was demonstrated during two conferences (2012 & 2014). Altogether, proposed studies will determine AAs serving as pH-sensor/s, and will allow to find whether pHi influence gj by acting on fast, slow, or both gates.
Funding: Project No. MIP-76/2015 was funded by Research Council of Lithuania.
Project duration: 2015 – 2017.
2. Project title: „Study of connexin 26 mutations in syndromic deafness“
Project objective: To improve professional skills of researchers with PhDs and encourage the planning and implementation of high level research projects.
Mutation of the connexin 26 (Cx26) gap junction (GJ) channel protein is the most common cause of congenital, sensorineural deafness in humans. Although studies have established that deletion of Cx26 from the cochlear sensory epithelium produces deafness, the role Cx26 plays to maintain hearing remains uncertain. Complicating an understanding of the role of Cx26 is two functional channel configurations that serve very different tissue functions. GJ channels are formed by the docking of two hemichannels and serve as pathways for direct electrical and chemical signaling between cells. Undocked hemichannels can also function and mediate signaling across the plasma membrane. A number of Cx26 missense mutations with retained channel function also cause deafness that is often syndromic, such as in keratitis-ichthyosis-deafness (KID) syndrome, in which hearing loss is accompanied by serious skin disorders. A leading hypothesis is that the pathogenesis of KID and other Cx26-linked syndromes is the result of aberrantly-functioning hemichannels that alter transmembrane signaling and compromise cell integrity. The common association of KID mutants with the aqueous pore suggests that altered permeability characteristics may be principal contributors to disease. Purinergic signaling and Ca2+play prominent roles in the cochlea and skin and here we investigate how two KID mutants, G45E and D50N, differentially affect Ca2+ influx, ATP release and subsequent signaling to adjacent cells. We use mammalian cell expression systems to quantify effects under conditions of defined Cx expression and coupling geometry. We extend to these studies to native cells using keratinocytes and cochlear explant cultures isolated from transgenic animals carrying the G45E mutation. Overall, we view that this work will have a major impact in understanding Cx26-linked syndromic deafness as well as a growing list of disorders in which aberrant Cx channels underlie tissue dysfunction.
Funding: Funded by European Union fund investment operational programme “09.3.3-LMT-K-712 Development of scientific competences of scientists, other researchers and students through practical research activities”.
Project duration: 2017-2019.
Postdoctoral fellow: Dr. Lina Rimkutė.
Fellowship supervisor: Prof. dr. Vytautas K. Verselis.
3. Project title: „Modeling voltage gating properties of gap junction channels, formed of connexin protein“
Funding: Project is being funged by science project competition award of the association „Santakos slėnis“.
Project duration: 2018-03-20 – 2018-12-31.
Publications of the research group:
The full list of Prof. habil. dr. Feliksas Bukauskas publications can be found here.
2016 - 2018
- Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions. Lina Rimkute, Tadas Kraujalis, Mindaugas Snipas, Nicolas Palacios-Prado, Vaidas Jotautis, Vytenis A. Skeberdis, Feliksas F. Bukauskas. Front. Physiol., 12 April 2018. https://doi.org/10.3389/fphys.2018.00362. Internet access
- Molecular basis for potenentiation of Cx36 gap junction channel conductance by n-alcohols and general anesthetics. Vytautas Raškevičius, Vaidas Jotautis, Lina Rimkutė, Alina Murandykina, Mintautė Kazokaitė, Visvaldas Kairys, Vytenis Arvydas Skeberdis. Bioscience Reports (2018) 38 BSR20171323. Published online 2018 Feb 8. Prepublished online 2018. doi: 10.1042/BSR20171323. Internet access
- Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating. Mindaugas Snipas, Lina Rimkute, Tadas Kraujalis, Kestutis Maciunas, Feliksas F. Bukauskas. PLoS computational biology. San Francisco: Public Library of Science. (Research article). ISSN 1553-734X. 2017, vol. 13, no. 4, p. 1-26. Internet access
- An acute mouse spinal cord slice preparation for studying glial activation ex vivo. Juan Mauricio Garré, Guang Yang, Feliksas F. Bukauskas, Michael V. L. Bennett. Bio-protocol. Sunnyvale, CA: Bio-protocol LLC. ISSN 2331-8325. 2017, vol. 7, no. 2, p. 1-10. Internet access
- Polyamines preserve connexin 43-mediated gap junctional communication during intracellular hypercalcemia and acidosis. Kucheryavykh Lilia Y, Benedikt Jan, Cubano Luis A, Skatchkov Serguei N, Bukauskas Feliksas F, Kucheryavykh Yuriy V. Neuroreport. Philadelphia: Lippincott Williams & Wilkins. ISSN 0959-4965. 2017, vol. 28, no. 4, p. 208-2013. Internet access
- Stochastic model of gap junctions exhibiting rectification and multiple closed states of slow gates. Mindaugas Snipas, Tadas Kraujalis, Nerijus Paulauskas, Kestutis Maciunas, Feliksas F. Bukauskas. Biophysical journal. Cambridge, MA: Cell Press. ISSN 0006-3495. 2016, vol. 110, no. 6, p. 1322-1333. Internet access
- Reverberation of excitation in neuronal networks interconnected through voltage-gated gap junction channels. Kestutis Maciunas, Mindaugas Snipas, Nerijus Paulauskas, Feliksas F. Bukauskas. Journal of general physiology. New York: Rockefeller University Press. (Research article). ISSN 0022-1295. 2016, vol. 147, iss. 3, p. 273-288. Internet access
- FGF-1 triggers pannexin-1 hemichannel opening in spinal astrocytes of rodents and promotes inflammatory responses in acute spinal cord slices. Juan Mauricio Garré, Guang Yang, Feliksas F. Bukauskas, Michael V. L. Bennett. Journal of neuroscience. Washington, DC: Society for Neuroscience. ISSN 0270-6474. 2016, vol. 36, no. 17, p. 4785-4801. Internet access
- The Role of neural connexins in HeLa cell mobility and intercellular communication through tunneling tubes. Lina Rimkutė, Vaidas Jotautis, Alina Marandykina, Renata Sveikatienė, Ieva Antanavičiūtė, Vytenis Arvydas Skeberdis. BMC cell biology. London: Biomed Central Ltd. (Research article). ISSN 1471-2121. 2016, vol. 17, no. 1, p. 1-12. Internet access
- Differences in the control of basal L-type Ca2+ current by the cyclic AMP signaling cascade in frog, rat, and human cardiac myocytes. Rimantas Treinys, Andrius Bogdelis, Lina Rimkutė, Jonas Jurevičius, Vytenis Arvydas Skeberdis. Journal of physiological sciences : JPS. Tokyo: Springer. (Original paper). ISSN 1880-6546. 2016, vol. 66, no. 4, p. 327-336. Internet access
2013 - 2015
- Application of stochastic automata networks for creation of continuous time markov chain models of voltage gating of gap junction channels. Mindaugas Snipas, Henrikas Pranevicius, Mindaugas Pranevicius, Osvaldas Pranevicius, Nerijus Paulauskas, Feliksas F. Bukauskas. BioMed research international. New York: Hindawi Publishing Corporation. (Research article). ISSN 2314-6133. 2015, vol. 2015, p. 1-13. Internet access
- Continuous time Markov chain models of voltage gating of gap junction channels. Henrikas Pranevicius, Mindaugas Pranevicius, Osvaldas Pranevicius, Mindaugas Snipas, Nerijus Paulauskas, Feliksas Bukauskas. Information technology and control = Informacinės technologijos ir valdymas / Kaunas: KTU. ISSN 1392-124X. 2014, vol. 43, no. 2, p. 133-142. Internet access
- Regulation of connexin-36 gap junction channels by n-alkanols and arachidonic acid. Marandykina A, Palacios-Prado N, Rimkute L, Skeberdis VA, Bukauskas FF. Journal of physiology. Oxford: Wiley. ISSN 0022-3751. 2013, vol. 591, part 8, p. 2087-2101. Internet access
- Magnesium-dependent modulation of junctional conductance and gating properties of Connexin36 Gap junction channels. Nicolas Palacios-Prado, Alina Marandykina, Lina Rimkute, Sandrine Chapuis, Nerijus Paulauskas, Vytenis A. Skeberdis, John O’Brien, Michael V.L. Bennett, Feliksas F. Bukauskas. Biophysical Journal : 57th Annual Meeting: February 2-6, 2013, Philadelphia, Pennsylvania / Biophysical Society. New York ; Cambridge: Biophysical Society Published by Elsevier Inc. (Wednesday, February 6, 2013.). ISSN 0006-3495. 2013, vol. 104, iss. 2, suppl. 1, p. 631a, no. 3245-Pos Board B400. Internet access