Ischemic injury activates PTHrP and PTH1R expression in human ventricular cardiomyocytes.
The PTHrP/PTH1R signalling system induces calciotropic and myorelaxant effects on the vascular system and plays critical roles in the development of the cardiovascular system. In animal models, PTHrP exerts important effects on heart rate and contractility, particularly under ischemic conditions, while, in human hearts, the expression of PTHrP by cardiomyocytes remains to be defined in both normal and ischemic conditions. The present study has been conducted on 101 autoptical cases and confirmed on nine explanted hearts in order to analyze the expression of the PTHrP/PTH1R system by ventricular myocardium in respect to morphological aspects of the myocardial ischemic damage, myofiber hypertrophy and disarray, coronarosclerosis, age and sex. Immunohistochemistry showed positive cytoplasmic immunostaining for both PTHrP and PTH1R in ventricular cardiomyocytes. The expression levels of the PTHrP/PTH1R system resulted significantly increased (P = 0.0008 and P < 0.0001, respectively) in association with the myocardial ischemic damage and the presence of cardiomyocyte hypertrophy (P = 0.02 and P = 0.009 respectively). Conversely, increased expression levels of PTHrP alone were observed in myofiber disarray (P = 0.04), whereas PTH1R was augmented in coronarosclerosis (P = 0.004) and age (P = 0.001). Taken together, these results demonstrate that human ventricular cardiomyocytes express PTHrP and PTH1R and suggest that the activation of the PTHrP/PTH1R system could represent an aspect of the embryonic gene program typically reactivated by the myocardium when subjected to ischemia and/or hypertrophy.
Monego
Giovanni
G
Dept. of Human Anatomy and Cell Biology, Università Cattolica del Sacro Cuore, Largo F. Vito, 1, 00168, Rome, Italy. giovanni.monego@rm.unicatt.it
Arena
Vincenzo
V
Pasquini
Sandra
S
Stigliano
Egidio
E
Fiaccavento
Roberta
R
Leone
Ornella
O
Arpesella
Giorgio
G
Potena
Luciano
L
Ranelletti
Franco Oreste
FO
Di Nardo
Paolo
P
Capelli
Arnaldo
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism*; D055815:Young Adult
C473449:PTH1R protein, human; D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1