The effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors on oxidative and hypoxic stress in the vascular endothelium

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) improve endothelial cell (EC) function by enhancing the synthesis of Nitric Oxide (NO) and attenuating the endothelial leucocyte interaction and platelet aggregation. However the effects of statins on endothelial cell proliferation, apoptosis and the mediators of these responses are not clearly defined.The aims of this research were: 1) To determine the effect of statin on EC proliferation and apoptosis. 2) To assess these cellular processes in the presence of oxidative stress and hypoxia. 3) To study the cellular response to these stresses in the presence of a statin. 4) To assess the effect of sudden withdrawal of statin on the endothelial cell proliferation and apoptosis.Statins exert a proliferative effect on EC at low concentrations and induce apoptosis at higher doses. Oxidative stress and hypoxia induce apoptosis in the EC, mediated via enhanced expression of an apoptotic protein, Bax. Statins abrogate the anti-proliferative and pro-apoptotic effects of oxidative and hypoxic stress by modulating the expression of Bax and cell cycle regulator protein Cyclin D. Acute withdrawal of statins reverses the protective effects on EC survival by promoting apoptosis and inhibiting the proliferative activity.

Name dc:type.qualificationname

MD

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Hull

Year dc:date.issued

2008

Author dc:creator

• Mylankal, Kurian Joseph

Advisor dc:contributor.advisor

• McCollum, Peter T.

• Medicine

Language dc:language

en

Identifier

oai:hull-repository.worktribe.com:4212332

OAI identifier oai:identifier

oai:hull-repository.worktribe.com:4212332