Chylomicronemia Elicits Atherosclerosis in Mice—Brief Report

Abstract

Objective— The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in Gpihbp1 -deficient mice ( Gpihbp1 −/− ), which manifest severe chylomicronemia as a result of defective lipolysis. Methods and Results— Gpihbp1 −/− mice on a chow diet have plasma triglyceride and cholesterol levels of 2812±209 and 319±27 mg/dL, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50 to 135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both Gpihbp1 -deficient “apo-B48–only” mice and Gpihbp1 -deficient “apo-B100–only” mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48– and apo-B100–containing lipoproteins. Conclusions— Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48– and apo-B100–containing lipoproteins.