Expression, release, and biological activity of parathyroid hormone-related peptide from coronary endothelial cells

Ventricular cardiomyocytes have previously been identified as potential tar get cells for parathyroid hormone-related peptide (PTHrP). Synthetic PTHrP peptides exert a positive contractile effect. Because systemic PTHrP levels are normally negligible, this suggests that PTHrP is expressed in the vent ricle and acts as a paracrine mediator. We investigated the ventricular exp ression of PTHrP and its expression in cultured cells isolated from the ven tricle, studied the release of PTHrP from hearts and cultures, and investig ated whether this authentic PTHrP mimics the biological effects previously described for synthetic PTHrP on ventricular cardiomyocytes. We found PTHrP expressed in ventricles of neonatal and adult rat hearts. In cells isolate d from adult hearts, we found PTHrP expression exclusively in coronary endo thelial cells but not in cardiomyocytes. The latter, however, are target ce lls for PTHrP. PTHrP was released from isolated perfused hearts during hypo xic perfusion and from cultured coronary endothelial cells under energy-dep leting conditions. This PTHrP was biologically active; ie, it exerted a pos itive contractile and lusitropic effect on cardiomyocytes, Authentic PTHrP was glycosylated and showed a slightly higher potency than synthetic PTHrP. These results suggest that PTHrP is an endothelium-derived modulator of ve ntricular function.