Inhibition of Local Macrophage Growth Ameliorates Focal Inflammation and Suppresses Atherosclerosis

Arteriosclerosis, Thrombosis, and Vascular Biology
Sarie YamadaEiichi Araki

Abstract

Macrophages play a central role in various stages of atherosclerotic plaque formation and progression. The local macrophages reportedly proliferate during atherosclerosis, but the pathophysiological significance of macrophage proliferation in this context remains unclear. Here, we investigated the involvement of local macrophage proliferation during atherosclerosis formation and progression using transgenic mice, in which macrophage proliferation was specifically suppressed. Inhibition of macrophage proliferation was achieved by inducing the expression of cyclin-dependent kinase inhibitor 1B, also known as p27kip, under the regulation of a scavenger receptor promoter/enhancer. The macrophage-specific human p27kip Tg mice were subsequently crossed with apolipoprotein E-deficient mice for the atherosclerotic plaque study. Results showed that a reduced number of local macrophages resulted in marked suppression of atherosclerotic plaque formation and inflammatory response in the plaque. Moreover, fewer local macrophages in macrophage-specific human p27kip Tg mice helped stabilize the plaque, as evidenced by a reduced necrotic core area, increased collagenous extracellular matrix, and thickened fibrous cap. These results provide dir...Continue Reading

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Citations

Jan 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Emiel P C van der Vorst, Christian Weber
Jul 25, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Jathushan PalasubramaniamKarlheinz Peter
Dec 24, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Nov 8, 2019·Molecular Nutrition & Food Research·Victoria L O'Morain, Dipak P Ramji
Mar 28, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Congqing WuHong S Lu
Feb 9, 2021·Free Radical Biology & Medicine·Hong WuQingbo Xu
Apr 22, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xinlong ZangXuehong Chen
Aug 3, 2021·Current Opinion in Lipidology·Michael T Patterson, Jesse W Williams

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