Abstract 668: Whole Body and Hematopoietic Sortilin Deficiency Reduces Atherosclerosis in Mice Independent of Effects on LDL Cholesterol

Background: Genetic variants on chromosome 1p13 at the SORT1 locus are genome-wide significantly associated with both LDL cholesterol as well as with myocardial infarction (MI). Sortilin, encoded by the SORT1 gene, traffics to both the Golgi as well as the plasma membrane, where it binds ligands and transports them to the lysosome. Our lab recently showed that sortilin is a high affinity receptor for LDL, and genetic manipulation of sortilin expression in the liver influences LDL-C levels. Sortilin is also expressed in macrophages but little is know about its function in this cell type or its relationship to atherosclerosis. Results: Sortilin deficient mice were crossed to atherosclerosis-prone Apobec-/-; human ApoB Tg mice. On this model, plasma total and LDL-C levels were not different in the sortilin deficient vs the wild-type mice. Unexpectedly, aortic atherosclerosis measured en face was reduced by 90% (n=10 per group; P = 5.3 E-7). To determine whether hematopoetic sortilin contributed to this effec...