Ca2+ Fluxes Involvement in Gene Expression During Cardiac Hypertrophy

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

Journal Name: Current Vascular Pharmacology

Volume 11 , Issue 4 , 2013

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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.

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

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Article Details

VOLUME: 11
ISSUE: 4
Year: 2013
Page: [497 - 506]
Pages: 10
DOI: 10.2174/1570161111311040013
Price: $65

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