Cardio-vascular activity of catestatin: interlocking the puzzle pieces.
Catestatin (CST), the Chromogranin A (CgA)-derived cationic and hydrophobic peptide, firstly recognized as an endogenous inhibitor of catecholamine secretion, functions as a physiological brake of the adreno-sympathetic-chromaffin system. Its wide spectrum of activities includes relevant multilevel cardiovascular and antihypertensive influences. At central systemic level, CST seems to modulate the autonomic cardiovascular control possibly acting on baroreceptor afferent fibers of the nucleus tractus solitarius. This, as well as clinical and experimental (CgA-KO mice) evidences point to an important role of CST in the determinism and prevention of essential hypertension. At organ level, CST exerts myocardial (negative inotropy and lusitropy) effects and potently vasodilates endothelin-1 (ET-1)-preconstricted coronaries through β2-adrenergic receptor (AR)-Gi/o protein-nitric oxide (NO)-cGMP signalling, while counterbalancing β adrenergic (ISO) stimulation. The contractile myocardial effects have been deeply analysed in fish and amphibian hearts, highlighting finely diversified mechanisms of action. CST also acts as cardioprotective agent in both pre- and post-conditioning through NO-dependent mechanisms implicating the Reperfusion Injury Salvage Kinase (RISK) signalling and the activation of mitoKATP channels. The CST-elicited cardiotropic and coronarotropic influences, along with the recently discovered proangiogenic and regulatory effects in glucose and lipid metabolism, contribute to delineate an integrated and updated picture of the peptide which emerges as a pleiotropic hormone with a wide range of cytokine-like characteristics. The aim of this review is to interlock some older and more recent evidences which may help to better perceive the subtle links and differences among the puzzle pieces that still need to be deciphered.
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Mazza
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Tota
Lab of Organ Physiology, Dept of Biology, Ecology and Earth Sciences, University of Calabria, 87036, Arcavacata di Rende (CS)- Italy. bruno.tota@unical.it.
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Gattuso
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D053379:Chromogranin A / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*
D002316:Cardiotonic Agents; D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364)