ADCY3, AGT, AKAP5, AKT1, CABIN1, CACNA1C, CACNA1G, CACNA1H, CACNA1S, CALM1, CALM2, CALM3, CAMK2A, CAMK2B, CAMK2G, CAMK4, CREBBP, CSNK1A1, EDN1, ELSPBP1, EP300, GATA4, GNA11, GNAI1, GNAI2, GNAI3, GNAQ, GNAS, GSK3B, HAND1, HAND2, HDAC1, HDAC2, HDAC3, HDAC4, HDAC6, HRAS, IGF1, IGF1R, IL11, IL6, IL6ST, ITPR1, ITPR3, KRAS, ...LIF, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K6, MAP3K1, MAP3K5, MAP3K7, MAPK1, MAPK10, MAPK12, MAPK13, MAPK14, MAPK3, MAPK8, MEF2A, MEF2C, NFATC4, NKX2-5, NRAS, PIK3CA, PIK3CD, PIK3R1, PIK3R2, PLCB1, PLCG1, PLCG2, PPP3CA, PRKACA, PRKAR1A, PRKAR2A, PRKAR2B, PRKCA, PRKCD, PRKCE, PRKCZ, RAF1, RCAN1, SCN1A, SCN5A, SCNN1A, SCNN1B, SCNN1G, SLC9A1, SOS1, SRC
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Cardiac failure is often associated with prolonged and maladaptive cardiac hypertrophy, defined as a compensatory mechanism of the heart that helps to maintain cardiac output during pathological states with sustained increases in hemodynamic load. As card ...iomyocytes lose the ability to divide soon after birth, cardiac hypertrophy offers an important adaptive response in vivo that allows the organism to maintain or increase its cardiac output. The adult myocardium responds to a wide array of intrinsic and extrinsic stimuli, including hypertension, myocardial infarction, cardiac arrhythmias, valvular disease, endocrine disorders, increased workload, injury, and contractile abnormalities resulting from mutant sarcomeric proteins by hypertrophic growth. Although initially beneficial, prolonged hypertrophy is correlated with poor clinical prognosis resulting in dilated cardiomyopathy, heart failure, and sudden death. The hypertrophic response is orchestrated by growth factors and cytokines acting through several interdependent signaling cascades, including, specific G-protein isoforms, low-molecular-weight GTPases (Ras), MAPK (Mitogen-Activated Protein Kinase) and PKC (Protein Kinase-C). In addition, recent studies have recognized the importance of Ca2+ sensitive signaling molecules, including calcineurin, CalmK (Calcium/Calmodulin-Dependent Protein Kinase), and MAPK in hypertrophic pathways, in which NFAT (Nuclear Factor Of Activated T-Cells) occupies the central place, being the best-characterized target for the development of cardiac hypertrophy. Initial phase in the development of myocardial hypertrophy involves the formation of cardiac para- and/or autocrine factors like Endothelin-1, Angiotensin-II, and the Adrenergic agonists: phenylephrine and norepinephrine, at the cell membrane, the receptors of which are coupled to G-Proteins of the G-AlphaQ/G-Alpha11, G-AlphaS, and G-AlphaI-families. Other receptors associated with the induction hypertrophy through the NFATC4 pathway include IGF1 (Insulin Like Growth Factor-1), GP130, etc.
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