EUGeneHeart: EUGeneHeart: Genomics of Cardiomyocyte Signalling to Treat and Prevent Heart Failure     

Coordinator: Gerd Hasenfuss
Team Leader: Alexandra Zahradníková

Duration: January 2006 – December 2010
Coordinating Organization: University of Gottingen, Germany


The project is aimed on genomics of the signalling mechanisms that play a role in heart failure, a disease very frequent in European population. The ultimate objective is to develop more effective treatment of this syndrome. Therefore the consortium involves laboratories and institutions that specialize in basic, pharmaceutical and clinical research, as well as SMEs. The project is based on the hypothesis that the changes in the structure and function of the heart that precede heart failure can be divided into beneficial (that improve cardiac function) and maladaptive (that lead to heart failure), and that it is possible to selectively inhibit maladaptive changes. The differences between subjects different in the predisposition to heart failure will be analyzed, genomic and proteomic screening performed, and the findings will be translated into pharmacological and clinical practice. The project has an important educational and training component (conferences, workshops).


Heart failure, hypertrophic signalling, cardiac myocyte


The goal of the EUGeneHeart project is the development of new approaches to prevent and treat heart failure through analysis of the genomics of signalling. The strategy is based on the hypothesis that beneficial as well as maladaptive forms of hypertrophy exist and that heart failure is frequently preceded by maladaptive hypertrophy. We will dissect both adaptive and maladaptive signalling in hypertrophy to identify beneficial and maladaptive components of signal transduction in hypertrophy and heart failure. (see

The team at the Department of Muscle Cell Research IMPG SAS will participate in determining, how and why is the ability of the heart to contract in response to electrical stimuli changed, and how are these changes affected by changes in gene expression and by drugs.


JGP Petrovic P, Valent I, Cocherova E, Pavelkova J, Zahradnikova A (2015): Ryanodine receptor gating controls generation of diastolic calcium waves in cardiac myocytes. J Gen Physiol 145: 489-511.
JGP Ghigo A, Perino A, Mehel H, Zahradníková A Jr, Morello F, Leroy J, Nikolaev VO, Damilano F, Cimino J, De Luca E, Richter W, Westenbroek R, Catterall WA, Zhang J, Yan C, Conti M, Gomez AM, Vandecasteele G, Hirsch E, Fischmeister R. (2012): Phosphoinositide 3-kinase ? protects against catecholamine-induced ventricular arrhythmia through protein kinase A-mediated regulation of distinct phosphodiesterases.. Circulation 126(17):2073-83.
CardiovascRes Piquereau J, Caffin F, Novotova M, Prola A, Garnier A, Mateo P, Fortin D, Huynh LH, Nicolas V, Alavi MV, Brenner C, Ventura-Clapier R, Veksler V, Joubert F (2012). Down-regulation of OPA1 alters mouse mitochondrial morphology, PTP function, and cardiac adaptation to pressure overload. Cardiovasc Res 94: 408-417.
JPhysiol3 Janicek R, Zahradnikova-Jr A, Polakova E, Pavelkova J, Zahradnik I, Zahradnikova A (2012): Calcium spike variability in cardiac myocytes results from activation of small cohorts of RYR2 channels. J Physiol 590: 5091-5106.
JGP Tencerova B, Zahradnikova A, Gaburjakova J, Gaburjakova M (2012): Luminal Ca2+ controls activation of the cardiac ryanodine receptor by ATP. J Gen Physiol 140: 93-108.
Nichtova Z, Novotova M, Kralova E, Stankovicova T (2012): Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol. Gen Physiol Biophys 31: 141-51.
JPhysiol3 Piquereau J, Novotova M, Fortin D, Garnier A, Ventura-Clapier R, Veksler V, Joubert F (2010). Postnatal development of mouse heart: formation of energetic microdomains. J Physiol.588: 2443-54.
JGP Zahradnikova A, Valent I, Zahradnik I (2010): Frequency and release flux of calcium sparks in rat cardiac myocytes: a relation to RYR gating. J Gen Physiol 136: 101-116.
JGP Zahradnikova A, Gaburjakova M Bridge JHB, Zahradnik I (2010): Challenging quantal calcium signaling in cardiac myocytes.. J Gen Physiol 136:581-583.
JPhysiol Polakova E, Zahradnikova A Jr, Pavelkova J, Zahradnik I, Zahradnikova A (2008). Local calcium release activation by DHPR calcium channel openings in rat cardiac myocytes. J Physiol. 586: 3839-3854.
JPhysiol Joubert F, Wilding JR, Fortin D, Domergue-Dupont V, Novotova M, Ventura-Clapier R, Veksler V (2008): Local energetic regulation of sarcoplasmic and myosin ATPase is differently impaired in rats with heart failure. J Physiol. 586: 5181-5192.
JPhysiol Athéa Y, Viollet B, Mateo P, Rousseau D, Novotova M, Garnier A, Vaulont S, Wilding JR, Grynberg A, Veksler V, Hoerter J, Ventura-Clapier R. (2007): AMP-activated protein kinase alpha2 deficiency affects cardiac cardiolipin homeostasis and mitochondrial function. Diabetes. 586: 786-794.
JPhysiol3 Zahradnikova A Jr, Polakova E, Zahradnik I, Zahradnikova A (2007). Kinetics of calcium spikes in rat cardiac myocytes. J Physiol 578: 677-691.