Over the last few years, the genetic and molecular basis of the disease has become an area of enormous interest. In our project, we are aiming to find new diagnostic markers with a high clinical clinical value. In addition to standard statistical methods, molecular methods – RT-PCR, Western blot analysis, Pathfast, ELISA – will be used to meet the targets.

The basic methodical steps of the methodologies used are known to the solving team. Thanks to the variety of methodologies and versatility of the team, we anticipate the successful integration of experimental results into clinical practice to identify the prediction of patient life. Molecular/cell imaging techniques, molecular biology, biochemistry, physiology, pharmacology and diagnostics will be used to target the prediction of cardiovascular injury progression in ISCH patients and ejection fraction randomization factors. The full participation of physicians-clinics allows for the anticipation of a successful potential therapeutic intervention. Obligatory for our molecular medical research will be the optimization of molecular biology methods from experimental conditions into real clinical practice and their subsequent interpretation for the possibility of timely prediction of the disease.

Thorough testing of specific genomic and proteomic methods will be performed in experimental clinical laboratories. The blood samples will be investigated for specific genes, proteins and microRNA, not only in the whole blood, but also in its individual parts (plasma, blood cells).

The decision-makers build on the work accomplishments of the individual members of the team, as well as on their long-term cooperation. Due to the fact that all members of the team are acquainted with each other, they are able to collaborate effectively and apply methodologies identifying molecular mechanisms and clinical aspects of individual patients involved in pathophysiological cascades of cardiovascular disease with targeting to ISCH with subsequent correlation of pharmacotherapy. For this purpose, RT-PCR, Western Blot Analysis, Immunology (ELISA) and Pathfast will be used. This project involves cooperation not only with the faculty of the Comenius University and the NICD clinic, but also with the unique international connection of experimental and clinical pharmacologists and doctors from the field of clinical pharmacology and cardiac surgery.

RT – PCR is a technique commonly used in molecular biology to detect RNA expression, measure the amplification of DNA using fluorescent dyes. We analyse with RT-CR microRNAs – miR-1, miR-29b, miR-133a, miR-214, miR-208a, miR-208b, miR-499 and E-selectin, ICAM1, NOS3, PECAM1, VCAM1.

Western blot (WB) is a widely used analytical technique used in molecular biology, immunogenetics and other molecular biology disciplines to detect specific proteins in a sample of tissue homogenate or extract. We analyse with WB proteins E-selectin, ICAM1, NOS3, PECAM1, VCAM1.

ELISA (enzyme-linked immunosorbent assay) is a test that uses antibodies and color change to identify a substance. Performing an ELISA involves at least one antibody with specificity for a particular antigen. We detect with ELISA angiotensin II, renin, ACE, CRP and IL-6 in blood samples.

Pathfast system combines the accuracy of a full-scale lab analyzer with the flexibility of a mobile solution. We detect with Pathfast hsCRP, NT-proBNP, D-dimer and troponin I.

In project we will used bioinformatics and statistic procedures that allow prediction of cardio – relevant microRNAs and specific biomarkers that may be involved in clinical outcomes of IHD. It should create the prediction algorithms, databases and data for data mining procedures.

The last period of our work is focused to stem cells therpapy of Cardiovasuclar diseases – clinical trials.

Huang ZP, Kataoka M, Chen J, Wu G, Ding J, Nie M, Lin Z, Liu J, Hu X, Ma L, Zhou B, Wakimoto H, Zeng C, Kyselovic J, Deng ZL, Seidman CE, Seidman JG, Pu WT, Wang DZ: Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis.  J Clin Invest. 2015 Nov 2;125(11):4122-34. doi: 10.1172/JCI82423. Epub 2015 Oct 5.

Huang ZP, Ding Y, Chen J1, Wu G, Kataoka M, Hu Y, Yang JH, Liu J, Drakos SG, Selzman CH, Kyselovic J, Qu LH, Dos Remedios CG1, Pu WT, Wang DZ: Long non-coding RNAs link extracellular matrix gene expression to ischemic cardiomyopathy. Cardiovasc Res. 2016 Nov 1;112(2):543-554. doi: 10.1093/cvr/cvw201.

Jinghai Chen, Masaharu Kataoka, Zhan-Peng Huan, Fei Gu, Jian Ding, Feng Gao, Tian Liang, Ning Liu, Feng Zhang, Qing Ma, Yingchao Wang, Mingming Zhang, Xiaoyun Hu , Jan Kyselovic, William T. Pu, Jian’an Wang, Da-Zhi Wang:Therapeutic role of miR-19a/19b in cardiac regeneration and protection from myocardial infarction” reference number: NCOMMS-17-22108C, Nature Communications, akceptované 2019.

Szobi, Adrián [UKOFAFT] (35%) – Goncalvesová, Eva (5%) – Varga, Zoltán (5%) – Leszek, Przemyslaw (5%) – Kusmierczyk, Mariusz (5%) – Hulman, Michal (5%) – Kyselovič, Ján [UKOFAFT] (5%) – Ferdinandy, Peter (5%) – Adameová, Adriana [KAUT] [UKOFAFT](30%): Analysis of necroptotic proteins in failing human hearts. In: Journal of Translational Medicine. – Vol. 15, Article Number 86 (2017), Nestr. [7 s.]. – ISSN 479-5876

Kyselovič, Ján (50%) – Varga, Ivan [UKOLFUHE] (50%): Research focused on microRNAs: A link between myocardial remodeling and growth during pathological processes and physical exercises In: Annals of Translational Medicine. – Vol. 5, Suppl. 1 (2017), Art. No. 20 [3 s.]. – ISSN 2305-5839

Rajtík, Tomáš [UKOFAFT] (15%) – Goncalvesová, Eva (10%) – Varga, Zoltán V. (10%) – Przemyslaw, Leszek (10%) – Kusmierczyk, Mariusz (10%) – Hulman, Michal (10%) – Kyselovič, Ján [UKOFAFT] (10%) – Adameová, Adriana [KAUT] [UKOFAFT] (15%) – Ferdinandy, Peter (10%): Posttranslational modifications of calcium/calmodulin-dependent protein kinase II? and its downstream signaling in human failing hearts.  In: American Journal of Translational Research. – Vol. 9, No. 8 (2017), s. 3573-3585. – ISSN 1943-8141

Polakovičová, Mája [UKOTVDKCH] (40%) – Musil, Peter (10%) – Laczo, Eugen [UKOTVKLA] (10%) – Hamar, Dušan [UKOTVKKA] (20%) – Kyselovič, Ján [UKOFAFT] (20%): Circulating microRNAs as potential biomarkers of exercise response. Lit. 130 zázn. In: International Journal of Molecular Sciences. – Roč. 17, č. 10, č. čl. 1553, (2016), s. 1-20. ISSN 1422-0067

Schuessler-Lenz, Martina (5%) – Beuneu, Claire (5%) – Menezes-Ferreira, Margarida (5%) – Jekerle, Veronika (5%) – Bartunek, Jozef (5%) – Chamuleau, Steven (5%) – Celis, Patrick (5%) – Doevendans, Pieter (5%) – O’Donovan, Maura (5%) – Hill, Jonathan(5%) – Hystad, Marit (5%) – Jovinge, Stefan (5%) – Kyselovič, Ján [UKOFAFT] (5%) – Lipnik-Stangelj, Metoda (5%) – Maciulaitis, Romaldas (5%) – Prasad, Krishna (4%) – Samuel, Anthony (4%) – Tenhunen, Olli (4%) – Tonn, Torsten (4%) – Rosano, Giuseppe (3%) -Zeiher, Andreas (3%) – Salmikangas, Paula (3%): Cell-based therapies for cardiac repair: a meeting report on scientific observations and European regulatory view pointsIn: European Journal of Heart Failure. – Vol. 18, No. 2 (2016), s. 133-141. – ISSN 1388-9842

Salmikangas, Paula (6%) – Menezes-Ferreira, Margarida (6%) – Reischl, Ilona (6%) – Tsiftsoglou, Asterios (6%) – Kyselovič, Ján [UKOFAFT] (10%) – Borg, John Joseph (6%) – Ruiz, Sol (6%) – Flory, Egbert (6%) – Trouvin, Jean-Hugues (6%) – Celis,Patrick (6%) – Ancans, Janis k (6%) – Timon, Marcos (6%) – Pante, Guido (6%) – Sladowski, Dariusz (6%) – Lipnik-Stangelj, Metoda (6%) – Schneider, Christian K. (6%): Manufacturing, characterization and control of cell-based medicinal products: challengingparadigms toward commercial use Lit. 63 zázn. In: Regenerative Medicine. – Vol. 10, No. 1 (2015), s. 65-78. – ISSN 1746-0751

Kyselovič, Ján [UKOFAFT] – Martinka, Peter – Baťová, Zuzana – Gažová, Andrea [UKOLFFAU] – Godfraind, Theophile: Calcium channel blocker inhibits western-type diet-evoked atherosclerosis development in apoEdeficient mice(S) In: Journal of Pharmacology and Experimental Therapeutics. – Vol. 315, No. 1 (2005), s. 320-328. – ISSN 0022-3565

Kyselovič, Ján [UKOFAFT] – Křenek, Peter, ml. [UKOFAFT] – Wibo, Maurice – Godfraind, Theophile: Effects of amlodipine and lacidipine on cardiac remodelling and renin production in salt-loaded stroke-prone hypertensive rats In: British Journal of Pharmacology. – Vol. 134, No. 7 (2001), s. 1516-1522. – ISSN 0007-1188

Kyselovič, Ján [UKOFAFT] – Morel, Nicol – Wibo, Maurice – Godfraind, Theophile: Prevention of Salt-Dependent Cardiac Remodeling and Enhanced Gene Expression in Stroke-Prone Hypertensive Rats by the Long-Acting Calcium Channel Blocker Lacidipine In: Journal of Hypertension. – Vol. 16, No. 10 (1998), s. 1515-1522. – ISSN 0263-6352

Kyselovič, Ján [UKOFAFT] – Leddy, J. J. – Ray, A. – Wigle, J. – Tuana, B. S.: Temporal differences in the induction of dihydropyridine receptor subunits and ryanodine receptors during skeletal muscle development: Journal of Biological Chemistry. – Vol. 269, No. 34 (1994), s. 21770-21777. – ISSN 0021-9258