Human catestatin peptides differentially regulate infarct size in the ischemic-reperfused rat heart.
In acute myocardial infarction increased plasma levels of chromogranin A are correlated with decreased survival. At the human chromogranin A gene locus there are two naturally occurring amino acid substitution variants within the catestatin region, i.e. Gly³⁶⁴Ser and Pro³⁷⁰Leu, displaying differential potencies towards inhibition of nicotinic cholinergic agonist-evoked catecholamine secretion from sympathochromaffin cells and different degrees of processing from the prohormone. Here, we examine whether two of the variants and the wild type catestatin may affect the development of infarct size during ischemic reperfusion in the Langendorff rat heart model. The hearts were subjected to regional ischemia followed by reperfusion in the presence or absence of synthetic variants of human catestatin. Compared to the Gly³⁶⁴Ser variant both the wild type and Pro³⁷⁰Leu variants increased infarct size while decreasing the cardiac levels of phosphorylated Akt and two of its downstream targets, FoxO1 and BAD. In conclusion, these findings suggest that, in contrast to the Gly³⁶⁴Ser variant, wild type catestatin and the Pro³⁷⁰Leu variant (allele frequency ~0.3%) increased myocardial infarct size via a mechanism involving dephosphorylation of Akt and the two downstream targets during ischemic reperfusion in the isolated rat heart.
Brar
Bhawanjit K
BK
Department of Medicine, UCSD, La Jolla, California, USA. bervy@yahoo.com
Helgeland
Erik
E
Mahata
Sushil K
SK
Zhang
Kuixing
K
O'Connor
Daniel T
DT
Helle
Karen B
KB
Jonassen
Anne K
AK
D000818:Animals; D002478:Cells, Cultured; D053379:Chromogranin A / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D053379:Chromogranin A; D010446:Peptide Fragments; C109084:chromogranin A (344-364)