Deficiency of scavenger receptor class B type 1 leads to increased atherogenesis with features of advanced fibroatheroma and expansive arterial remodeling.

Abstract

BACKGROUND: Scavenger receptor class B type 1 (SR-BI) is the main high-density lipoprotein (HDL) receptor in mammalians. Loss of SR-BI has been proven to disturb HDL metabolism and accelerate atherosclerosis. However, little is known about the plaque features and arterial remodeling in the increased atherogenesis caused by SR-BI deficiency. Here, we explored this issue in atherosclerosis-prone low-density lipoprotein receptor (LDL-R) knockout (KO) mice deficient of SR-BI. METHODS AND RESULTS: SR-BI/LDL-R double KO (dKO) and control LDL-R KO mice were fed an atherogenic diet for 12 weeks. Compared with the plaques in the LDL-R KO controls, which were lipid-dominant and collagen-poor, the plaques in the dKO mice were significantly enlarged, with a massive accumulation of collagen but no significantly increased infiltration of lipids, macrophages, or smooth muscle cells. In addition, the plaques in the brachiocephalic sinus of the dKO mice typically contained a necrotic core topped with a thin fibrotic cap. The increased atherogenesis in the dKO mice led to a following expansion of the vessel walls; therefore, the lumen area in the dKO mice was even slightly enlarged. CONCLUSION: We showed here that SR-BI deficiency led to increased atherogenesis with features of advanced fibroatheroma and expansive arterial remodeling in LDL-R KO mice fed an atherogenic diet.