期刊
CURRENT VASCULAR PHARMACOLOGY
卷 11, 期 4, 页码 497-506出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1570161111311040013
关键词
Heart; calcium; excitation-transcription coupling; cardiac hypertrophy
资金
- Inserm
- ANR [Geno-09-012, Geno-09-034]
- CODDIM [COD 100256]
- FRM [DPC20111122995]
- grant ANR Investissements d'avenir
- Ministerio de Economia y Competitividad in Juan de la Cierva postdoctoral program, Spain
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. beta-adrenergic receptor (beta-AR) produces cAMP, which directly, (through cAMP response element) or indirectly (through activating Epac) induces cardiac hypertrophy. alpha 1 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.
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