Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy

Title:Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy

Volume: 11 Issue: 4

Author(s): Ana M. Gomez, Gema Ruiz-Hurtado, Jean-Pierre Benitah and Alejandro Dominguez-Rodriguez

Affiliation:

Keywords: Heart, calcium, excitation-transcription coupling, cardiac hypertrophy.

Abstract: Cardiac hypertrophy arises as a response of the heart to many different pathological stimuli that challenge its work. Regardless of the initial pathologic cause, cardiac hypertrophy shares some characteristics resulting from a genetic reprogramming of several proteins. Recent studies point to Ca2+ as a key signaling element in the initiation of this genetic reprogramming. In fact, besides its important role in excitation-contraction coupling, Ca2+ regulates cardiac growth by activation of Ca2+-dependent transcription factors. This mechanism has been termed excitation-transcription (ET) coupling. Some information about cardiac ET coupling is being gathered from the analysis of cardiac hypertrophy development, where two Ca2+ dependent enzymes are key actors: the Ca2+/calmodulin kinase II (CaMKII) and the phosphatase calcineurin, both activated by Ca2+/Calmodulin. In this review we focus on some neurohormonal signaling pathways involved in cardiac hypertrophy, which could be ascribed as activators of ET coupling, for instance, adrenergic stimulation and the renin-angiotensin-aldosterone system. β-adrenergic receptor (β-AR) produces cAMP, which directly, (through cAMP response element) or indirectly (through activating Epac) induces cardiac hypertrophy. α1 AR and angiotensin receptor type 1 are Gq protein coupled receptors, which when activated, stimulate phospholipase C producing inositol 1,4,5 triphosphate (IP3) and diacylglycerol (DAG). IP3 promotes elevation of [Ca2+] in the nucleus, activating CaMKII/MEF2 (myocyte enhancer factor 2) pathway and may indirectly induce Ca2+ entry through transient receptor potential channels (TRPC). Other TRPC channels are activated by DAG. Ca2+ entry activates calcineurin/NFAT hypertrophic signaling. By promoting L-type Ca2+ channel expression, aldosterone may also have an important role in the genetic reprogramming during hypertrophy.

Cite this article as:

Gomez M. Ana, Ruiz-Hurtado Gema, Benitah Jean-Pierre and Dominguez-Rodriguez Alejandro, Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy, Current Vascular Pharmacology 2013; 11 (4) . https://dx.doi.org/10.2174/1570161111311040013