Title:Cardio-vascular Activity of Catestatin: Interlocking the Puzzle Pieces
Volume: 22
Issue: 3
Author(s): R. Mazza, B. Tota and A. Gattuso
Affiliation:
Keywords:
Cardioprotection, chromogranin A, myocardial performance, signal transduction, vertebrate heart.
Abstract: 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.
