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The cardioprotective effects of CST is also preserved in a mode of cardiac hyper-
trophy, a model usually not protected by ischemic conditioning protocols (Ma et al.
2013 ; Penna et al. 2010a, 2011a, b; Wagner et al. 2013 ). CST, in fact, resulted car-
dioprotective in isolated heart obtained from Spontaneously Hypertensive Rat. In
particular, in this model CST displayed an anti-apoptotic effect and induced the
expression of pro-angiogenetic factors (i.e., HIF-1α and eNOS expression) after 2 h
of reperfusion (Penna et al. 2014 ; Perrelli et al. 2013 ). Importantly, the chronic
administration of catestatin results to be protective after myocardial ischemia in
rats. In this chronic model the protective effect of CST may derive from its ability
to decrease the cardiac sympathetic drive and to improve autonomic function (Wang
et al. 2016 ).
3.3 Chromofungin
Recently Angelone and coworkers have demonstrated that another fragment of CgA,
chromofungin (Chr: CgA47-66) displays cardioprotective effects. Chr presents an
immediate protective anti-microbical effect (Metz-Boutigue et al. 2003 ), and the
ability to penetrate the cell membrane, thus inducing extracellular calcium entry by
a Calmodulin-regulated iPLA2 pathway (Zhang et al. 2009 ). Chr induces cardiopro-
tective effects acting as a post-conditioning agent through the activation of the RISK
pathways and via the involvement of mitoKAT P channels. In particular, the protective
effect of Chr was cGMP-dependent (Filice et al. 2015 ). Of note, this study has been
the first one that demonstrated a correlation between this cyclic nucleotide and car-
dioprotection by CgA fragments. This is important because cGMP plays a central
role in cardioprotection. In fact, PostC depends on GC activation via either NOS-
dependent or NOS-independent pathways (Penna et al. 2006a, b).
Another interesting aspect of the cardioprotective effects mediated by Chr is the
capacity to increase miRNA-21 expression. This effect has been correlated to the
reduction of infarct size, and the inhibition of pro-apoptotic genes and the increase
of anti-apoptotic genes (Cheng et al. 2009 ; Dong et al. 2009 ).
3.4 Serpinin
Recently, another CgA fragment, serpinin (Serp), has been studied on its ability to
induce cardioprotective effects. Interestingly, this fragment has been shown to exert
cardioprotective effects in both healthy and hypertensive rat heart models (Pasqua
et al. 2015 ). Perhaps more importantly, Serp, differently from other CgA fragments,
has been highly protective both in pre- and in post-conditioning protocols (Pasqua
et al. 2015 ). The cardioprotective effects of serpinin is mediated by an intracellular
signaling which, starting from β1-adrenergic receptor, includes adenylate cyclase
C. Penna and P. Pagliaro