Sortilin, Encoded by the Cardiovascular Risk Gene SORT1, and Its Suggested Functions in Cardiovascular Disease

被引:61
作者
Kjolby, Mads [1 ,2 ,3 ,4 ]
Nielsen, Morten Schallburg [1 ]
Petersen, Claus Munck [1 ]
机构
[1] Aarhus Univ, Lundbeck Fdn Res Ctr MIND, Aarhus, Denmark
[2] Danish Diabet Acad, Odense, Denmark
[3] Nord EMBL Partnership Mol Med, Danish Res Inst Translat Neurosci, Aarhus, Denmark
[4] Aarhus Univ Hosp, Dept Cardiol, DK-8000 Aarhus, Denmark
关键词
SORT1; Sortilin; PCSK9; IL6; TNF; LDL-cholesterol; GENOME-WIDE ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; NEUROTROPHIN RECEPTOR SORTILIN; CORONARY-ARTERY-DISEASE; SORTILIN/NEUROTENSIN RECEPTOR-3; MYOCARDIAL-INFARCTION; LIPID CONCENTRATIONS; LDL-CHOLESTEROL; VPS10P DOMAIN; LOCI;
D O I
10.1007/s11883-015-0496-7
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Several genome-wide association studies have linked novel loci to a wide range of cardiovascular phenotypes including low-density lipoprotein (LDL)-cholesterol, early onset myocardial infarction, coronary artery calcification, coronary artery stenosis, and abdominal aorta aneurysm. Especially, one locus, namely, 1p13.3, has attracted much attention. This locus harbors four candidate genes, CELSR2, PSRC1, MYBPHL, and SORT1. SORT1 encodes sortilin, a type I sorting receptor that has recently been implicated in LDL-cholesterol metabolism, VLDL secretion, PCSK9 secretion, and development of atherosclerotic lesions. Furthermore, sortilin also seems to be involved in the development of atherosclerosis, by mechanisms not directly involving LDL-cholesterol, but possibly resulting from the attenuated secretion of proinflammatory cytokines, such as IL6 and TNF alpha, which accompanies lack of sortilin in immune cells. Sortilin seems to play an important role in the development of cardiovascular disease and have functions beyond regulating LDL-cholesterol.
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页数:9
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