Myeloid Acyl-CoA:Cholesterol Acyltransferase 1 Deficiency Reduces Lesion Macrophage Content and Suppresses Atherosclerosis Progression.

The Journal of Biological Chemistry
Li-Hao HuangTa-Yuan Chang

Abstract

Acyl-CoA:cholesterol acyltransferase 1 (Acat1) converts cellular cholesterol to cholesteryl esters and is considered a drug target for treating atherosclerosis. However, in mouse models for atherosclerosis, global Acat1 knockout (Acat1(-/-)) did not prevent lesion development. Acat1(-/-) increased apoptosis within lesions and led to several additional undesirable phenotypes, including hair loss, dry eye, leukocytosis, xanthomatosis, and a reduced life span. To determine the roles of Acat1 in monocytes/macrophages in atherosclerosis, we produced a myeloid-specific Acat1 knockout (Acat1(-M/-M)) mouse and showed that, in the Apoe knockout (Apoe(-/-)) mouse model for atherosclerosis, Acat1(-M/-M) decreased the plaque area and reduced lesion size without causing leukocytosis, dry eye, hair loss, or a reduced life span. Acat1(-M/-M) enhanced xanthomatosis in apoe(-/-) mice, a skin disease that is not associated with diet-induced atherosclerosis in humans. Analyses of atherosclerotic lesions showed that Acat1(-M/-M) reduced macrophage numbers and diminished the cholesterol and cholesteryl ester load without causing detectable apoptotic cell death. Leukocyte migration analysis in vivo showed that Acat1(-M/-M) caused much fewer leukocyt...Continue Reading

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Jul 13, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Li-Hao HuangTa-Yuan Chang

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Citations

Mar 20, 2018·Journal of Lipid Research·Yuyan ZhuKee-Hong Kim
Mar 17, 2017·Journal of Lipid Research·Ta-Yuan ChangCatherine Chang
Mar 14, 2018·American Journal of Physiology. Endocrinology and Metabolism·Li-Hao HuangTa-Yuan Chang
Oct 5, 2018·Journal of Atherosclerosis and Thrombosis·Hisataka YamazakiShun Ishibashi
Apr 24, 2020·Circulation Research·Joshua J ManIris Z Jaffe
Sep 27, 2019·Pharmacological Reviews·Dongdong WangAtanas G Atanasov
Oct 5, 2018·Frontiers in Endocrinology·Yoshio Yamauchi, Maximillian A Rogers
Apr 14, 2018·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Yifeng WangTiangang Li
Oct 9, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Mengdie LuoJonathan D Smith

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