Sortilin: A novel regulator in lipid metabolism and atherogenesis.
Several lines of evidence have shown that SORT1 gene within 1p13.3 locus is an important modulator of the low-density lipoprotein-cholesterol (LDL-C) level and atherosclerosis risk. Here, we summarize the effects of SORT1, which codes for sortilin, on lipid metabolism and development of atherosclerosis and explore the mechanisms underlying sortilin effects on lipid metabolism especially in hepatocytes and macrophages. Recent epidemiological evidence demonstrated that sortilin has been implicated as the causative factor and regulates lipid metabolism in vivo. Hepatic sortilin overexpression leads to both increased and decreased LDL-C levels by several different mechanisms, suggesting the complex roles of sortilin in hepatic lipid metabolism. Macrophage sortilin causes internalization of LDL and probably a reduction in cholesterol efflux, resulting in the intracellular accumulation of excessive lipids. In addition, sortilin deficiency in an atherosclerotic mouse model results in decreased aortic atherosclerotic lesion. Sortilin involves in lipid metabolism, promotes the development of atherosclerosis, and possibly becomes a potential therapeutic target for atherosclerosis treatment.
Laboratory of Clinical Anatomy, University of South China, Hengyang 421001, China.
Li-Yuan
LY
Zhong
Department of Surgery, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5, Canada.
Francisco S
FS
Cayabyab
Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, Life Science Research Center, University of South China, Hengyang 421001, China.
Chao-Ke
CK
Tang
Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta T2N 4N1, Canada.
Xi-Long
XL
Zheng
Laboratory of Clinical Anatomy, University of South China, Hengyang 421001, China. Electronic address: thpeng67@163.com.
Tian-Hong
TH
Peng
Laboratory of Clinical Anatomy, University of South China, Hengyang 421001, China. Electronic address: anthony0723@163.com.
Yun-Cheng
YC
Lv
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000502:physiology*; D000818:Animals; D050197:Atherosclerosis; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008264:Macrophages / Q000378:metabolism; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D008078:Cholesterol, LDL; D000099183:Sortilin
Atherosclerosis; Lipid metabolism; Low-density lipoprotein; Sortilin