Journal article

Publication year: 2009

Pages: 493-502

Journal: Cellular Physiology and Biochemistry

Volume number: 24

Issue number: 5-6

ISSN: 1015-8987

eISSN: 1421-9778

Open access status: Bronze

DOI Link: https://doi.org/10.1159/000257492

Publisher: Karger Publishers Open Access

Abstract: 
Background: An increased susceptibility of microvascular 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 alpha(1)-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-beta(1) (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. Copyright (C) 2009 S. Karger AG, Basel

Harvard Citation style: Conzelmann, C., Krasteva, G., Weber, K., Kummer, W. and Schlueter, K. (2009) Parathyroid Hormone-Related Protein (PTHrP)-Dependent Regulation of bcl-2 and Tissue Inhibitor of Metalloproteinase (TIMP)-1 in Coronary Endothelial Cells, Cellular Physiology and Biochemistry, 24(5-6), pp. 493-502. https://doi.org/10.1159/000257492

APA Citation style: Conzelmann, C., Krasteva, G., Weber, K., Kummer, W., & Schlueter, K. (2009). Parathyroid Hormone-Related Protein (PTHrP)-Dependent Regulation of bcl-2 and Tissue Inhibitor of Metalloproteinase (TIMP)-1 in Coronary Endothelial Cells. Cellular Physiology and Biochemistry. 24(5-6), 493-502. https://doi.org/10.1159/000257492