Expression von Parathormone-related Peptide in koronaren Endothelzellen und der glatten Gefäßmuskulatur
Abstract
Parathyroid hormone related peptide (PTHrP) is expressed throughout the vascular system including coronary endothelial cells. The regulation of endothelial PTHrP expression and the role of PTHrP expression in endothelial cells is not clear. The present study investigates the question whether stimulation of a-adrenergic or angiotensin II receptors increases endothelial expression of PTHrP and whether endogenously expressed PTHrP exerts intracrine effects in coronary endothelial cells. It was found that stimulation of alpha1A-adrenoceptors, but not that of angiotensin II, increases cellular expression of PTHrP in growing, but not in growth arrested, coronary endothelial cells. Angiotensin II increases the expression of PTHrP in smooth muscle cells, but not in endothelial cells. PTHrP enters the nucleus of endothelial cells at the stadium of confluence. This suggests an intracrine effect of PTHrP. It was further investigated whether downregulation of endogenous PTHrP expression by transfection with antisense oligonucleotides alters cell proliferation or apoptosis resistance in growing or non-growing endothelial cells. Downregulation of PTHrP did not modify cell proliferation but increased the amount of UV-induced apoptosis. An increased expression of PTHrP in cells pre-treated with an a-adrenoceptor agonist reduced basal rate of apoptosis and improved resistance against UV-induced apoptosis. These results indicate a novel intracrine effect of PTHrP in coronary endothelial cells that improves cell survival. In endothelial cells, the expression of PTHrP is regulated by alpha-adrenoceptor stimulation in a cell-cycle dependent and cell-type specific manner.
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