Publisher: Karger
E-ISSN: 1421-9778|24|5-6|493-502
ISSN: 1015-8987
Source: Cellular Physiology and Biochemistry, Vol.24, Iss.5-6, 2009-11, pp. : 493-502
Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.
Abstract
Background: An increased susceptibility of micro-vascular endothelial cells to apoptosis is considered to be an initial event leading to atherosclerosis. Parathyroid hormone-related peptide (PTHrP) is known to protect endothelial cells against apoptosis by the regulation of the anti-apoptotic gene bcl-2. As tissue inhibitor of metalloproteinase (TIMP-1) expression is regulated by bcl-2, we hypothesized that endothelial expression of PTHrP also regulates the expression of TIMP-1. Methods: The steady state mRNA expressions of bcl-2, bax, TIMP-1, and TIMP-2 were analyzed by real-time RT-PCR and their protein expression by immunoblotting. The tissue distribution of PTHrP was investigated in cryosections of hearts from normotensive and hypertensive rats. Results: Phenylephrine, an α1-adrenoceptor agonist, increased the expression of PTHrP, bcl-2, and TIMP-1. Transfection of endothelial cells with oligonucleotides directed against PTHrP attenuated this effect. Antisense transfection and TGF-β1 (10 ng/ml) decreased the expression of PTHrP, bcl-2, TIMP-1, and TIMP-2, but not that of bax. Endothelial cells were identified as the main source of PTHrP in the heart. Endothelial cells in hearts from spontaneously hypertensive rats showed reduced staining with a PTHrP antibody compared to control normotensive hearts. Conclusions: These data suggests that the down-regulation of PTHrP favours atherosclerosis in chronic pressure overload.
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