Chromogranins from Cell Biology to Physiology and Biomedicine

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cardiomyoblasts with Anoxia/Reoxygenation (A/R) protocol. In this model the
siRNA-mediated knockdown of catestatin exaggerated endoplasmic reticulum stress
induced apoptosis. This protective effect is dependent on ERK1/2/PI3K/Akt path-
way. In particular, the protective effect of catestatin may depend on the activation of
type 2 Muscarinic receptor, and seems independent of type 1 Muscarinic receptor
activation (Liao et al. 2015 ). Despite the aforementioned studies report a cardiopro-
tective effects for CST in different models, Brar et al. ( 2010 ) described deleterious
effects against I/R injury for both the wild type and Pro^370 Leu variants of CST, but
not for Gly^364 Ser variant. These authors studied these three different variants of CST
in the isolated perfused rat hearts subjected to regional ischemia and the CTSs were
administered during the entire period of reperfusion. These different results might be
explained on the basis of the different models investigated (isolated rat heart perfused
at constant pressure and subjected to regional ischemia vs hearts perfused at constant
flow and subjected to global ischemia), the modality of administration of CST (the
entire reperfusion period or the first 20 min of reperfusion, when the majority of I/R
injury occurs) and the dose used (75 nM for 20 min vs 100 nM for 120 min). Finally,
it is noteworthy that in the setting of isolated hearts, when studying I/R injury, ven-
tricular volume adjustment is crucial part of maintaining a good heart preparation
and the subsequent interpretation of data obtained. We usually pierce the left ventri-
cle and set the volume of the balloon to obtain an end diastolic left ventricular pres-
sure (LVDP) below 5 mmHg (Penna et al. 2006a, 2007 , 2014 ; Perrelli et al. 2013 ),
whereas Brar et al. ( 2010 ) imposed an LVDP of 5–10 mm Hg. This higher range of
LVDP may have affected the amount of myocardial necrosis. “The volume of the
balloon should be such that it is able to fill the ventricular cavity; ... too large and the
potential for inducing endocardial necrosis once a pre-load diastolic pressure is set”
(Bell et al. 2011 ).

Ischemia/Reperfusion Injury

CgA peptides

(Vasostatin, Catestatin,

Serpinine and Chromofungin)

(Necrosis, Apoptosis

Contractile dysfunction

Heart failure)

Reduction of infarct size

Reduction of cardiac dysfunction

Reduction of apoptosis

Expression of NOS

Expression of miRNA-21

In healthy and hypertrophy cardiac models

Fig. 3 Scheme depicting the main outcomes of cardiac ischemia/reperfusion injury (IRI) and the
main cardioprotective results obtained with CgA-derived peptides in this context. The IRI leads to
heart failure, the CgA-derived peptides limits IRI and increase the expression of protective factors
in healthy and hypertrophy cardiac model. See text for further explanation

Cardioprotection and Chromogranin A-Derived Peptides