185and cAMP/PKA pathway, with a consequent phosphorylation of ERK1/2 and
GSK3β, which are components of RISK cardioprotective cascade. This promising
cardioprotective factor deserves to be studied more thoroughly.
4 Conclusions
It is conceivable that the effects of CgA and its derived fragments may be multifunc-
tional. In fact, on cardiovascular system they act not only via the nervous and sym-
pathoadrenal systems, but also via direct timely protective mechanisms on
endothelium and cardiomyocytes.
Interestingly, all studied fragments are cardioprotective, some are more effective
as preconditioning mediator (VS-1), other as postconditioning agent (CST) and
other as both pre- and post-conditioning inducer (Serp). As a matter of fact, delayed
increased levels of CST after infarction (O’Connor et al. 2002 ; Wang et al. 2011 ) are
in line with an attempt of compensatory protective response against cardiac injury
(Ceconi et al. 2002 ; Helle et al. 2007 ; Omland et al. 2003 ). Early interventions
which target the first few minutes of reperfusion, such as pharmacological postcon-
ditioning, may be clinically useful at the time of angioplasty, thrombolysis or car-
diac surgery. Importantly, VS-1 (Cappello et al. 2007 ; Cerra et al. 2008 ; Gallo et al.
2007 ; Ramella et al. 2010 ), CST (Angelone et al. 2008 ; Bassino et al. 2015 ; Penna
et al. 2010a, 2014 ; Perrelli et al. 2013 ) and Serp (Pasqua et al. 2015 ) positively influ-
ence endothelial function, and this may be of pivotal importance in organ protec-
tion. Our studies on cardioprotection also provide insights into the importance of
the stimulus-secretion associating CgA and its processing as an attempt of the car-
diovascular system to protect itself against I/R injury and associated patho-
physiological events. Altogether, our results suggest that CgA derived peptides
might represent a class of compounds dedicated to reduce cardiac reperfusion injury
in a time dependent fashion.
Acknowledgments The authors were funded by: National Institutes of Cardiovascular Research
(INRC) - Italy; Regione Piemonte, PRIN, ex-60% and Compagnia di San Paolo. We thank Prof.
Donatella Gattullo for her invaluable support.
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Cardioprotection and Chromogranin A-Derived Peptides