Title

The role of phospholipase C beta 3 in atherosclerosis

Date of Completion

January 2007

Keywords

Biology, Genetics|Biology, Cell

Degree

Ph.D.

Abstract

Although G protein coupled signaling is known to be essential in the initiation and progression of atherosclerosis, the contributions of its downstream signaling components to atherogenesis are largely unknown. This work shows that phospholipase C beta 3 is the major phospholipase C isoform in mouse macrophage, deficiency of which leads to significant reduction of atherosclerotic lesion. At cellular level, we further attribute reduction of atherogenesis to elevated macrophage apoptosis in response to oxidized LDL and oxysterol. As the molecular mechanisms, we found that phospholipase C beta 3 is required for sphingosine-1-phosphate mediated Bcl-xL upregulation and p21 activated kinase 1 suppression, both of which will lead to elevated cell death. ^