1711 Introduction
Several endogenous cardioprotective factors, including gasotransmitters nitric
oxide, hydrogen sulphide and carbon monoxide, as well as microvesicles and exo-
somes, may induce cardioprotection. Moreover, the cardioprotective effects may be
elicited by growth factors, cytokines and many endogenous peptides, like natriuretic
peptides, bradykinin, opioids and ghrelin-associated peptides (Garcia-Dorado et al.
2009 ; Penna et al. 2015 ). Among emerging peptides in the cardiovascular system,
chromogranin A (CgA) derived peptides are occupying a role of paramount
importance.
CgA is a key player in neuroendocrine regulation of cardiac function. (Aardal
and Helle 1992 ; Angeletti et al. 1994 ; Helle et al. 2001 , 2007 ; Pieroni et al. 2007 ).
Intriguingly, human ventricular myocardium produces and releases CgA and brain
natriuretic peptide (BNP), and, in fact, there is strong correlation between BNP and
CgA circulating levels in heart failure patients. Therefore, CgA may be a potential
therapeutic target in heart failure (Helle 2004 ) and CgA derived peptides may play
a role in regulating cardiovascular function. Moreover, CgA is emerging as a prog-
nostic marker. For instance, in a cohort of elderly patients with typical symptoms of
heart failure, it was demonstrated that the plasma level of CgA is a good marker of
death; in fact, it identifies those patients at increased risk of short- and long-term
mortality (Goetze et al. 2014 ). This aspect of CgA as new marker may have a clini-
cal relevance when the natriuretic peptide, a classical marker, is below the diagnos-
tic cutoff values (≤400 ng/l) proposed by European Society of Cardiology Guidelines
2008 (Goetze et al. 2014 ). The role of CgA as Heart Failure marker has also been
proposed by a recent echocardiographic study conducted on 112 patients (≥60 years
old) with normal Ejection Fraction (18 controls and 94 with hypertension). In this
study, the CgA levels resulted increased in subject with diastolic dysfunction respect
to controls (Szelényi et al. 2015 ).
As said, CgA is a precursor of several active peptides. In fact, a proteolytic pro-
cessing gives rise to several peptides of biological importance (Aardal et al. 1993 ;
Filice et al. 2015 ; Hou et al. 2016 ; Mahata et al. 1997 , 1999 , 2000 , 2003 , 2004 ;
Pasqua et al. 2015 ; Tatemoto et al. 1986 ) (For more details, see other chapters in this
book). Catestatin (CST), Vasostatin 1 (VS-1), Vasostatin 2 (VS-2) and Serpinin
(Serp) are CgA derivatives involved in the control of cardiovascular homeostasis.
These fragments of CgA present different and significative cardiac effects, ranging
from negative to positive inotropic effects, and their levels may be indicative of
pathological conditions such as left ventricular hypertrophy or metabolic syndrome.
Actually, Meng et al. ( 2011 ) have observed that in hypertensive patients the ratio of
Catestatin to Norepinephrine was lower in patients with left ventricular hypertrophy
respect to patients without hypertrophy; these results suggest that CST modulates
the cardiac hypertrophic response to high blood pressure. However, for instance, the
levels of VS-2 are significantly reduced in patients with important atherosclerosis
lesions (Cappello et al. 2007 ). Clearly, CgA and its derived peptides have a role in
the pathogenesis of hypertension, being a complex system able to modulate
Cardioprotection and Chromogranin A-Derived Peptides