Phospholipase C β3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice
Zhenglong Wang, … , Jonathan D. Smith, Dianqing Wu
Zhenglong Wang, … , Jonathan D. Smith, Dianqing Wu
Published December 13, 2007
Citation Information: J Clin Invest. 2008;118(1):195-204. https://doi.org/10.1172/JCI33139.
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Research Article Cardiology

Phospholipase C β3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice

Abstract

Atherosclerosis is an inflammatory disease that is associated with monocyte recruitment and subsequent differentiation into lipid-laden macrophages at sites of arterial lesions, leading to the development of atherosclerotic plaques. PLC is a key member of signaling pathways initiated by G protein–coupled ligands in macrophages. However, the role of this enzyme in the regulation of macrophage function is not known. Here, we studied macrophages from mice lacking PLC β2, PLC β3, or both PLC isoforms and found that PLC β3 is the major functional PLC β isoform in murine macrophages. Although PLC β3 deficiency did not affect macrophage migration, adhesion, or phagocytosis, it resulted in macrophage hypersensitivity to multiple inducers of apoptosis. PLC β3 appeared to regulate this sensitivity via PKC-dependent upregulation of Bcl-XL. The significance of PLC β signaling in vivo was examined using the apoE-deficient mouse model of atherosclerosis. Mice lacking both PLC β3 and apoE exhibited fewer total macrophages and increased macrophage apoptosis in atherosclerotic lesions, as well as reduced atherosclerotic lesion size when compared with mice lacking only apoE. These results demonstrate what we believe to be a novel role for PLC activity in promoting macrophage survival in atherosclerotic plaques and identify PLC β3 as a potential target for treatment of atherosclerosis.

Authors

Zhenglong Wang, Bei Liu, Ping Wang, Xuemei Dong, Carlos Fernandez-Hernando, Zhong Li, Timothy Hla, Zihai Li, Kevin Claffey, Jonathan D. Smith, Dianqing Wu

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