on October 8, 2009
Published online before print October 8, 2009, doi: 10.1161/ATVBAHA.109.196329
Submitted on November 20, 2008
Accepted on September 24, 2009
Chylomicronemia Elicits Atherosclerosis in Mice
Michael M. Weinstein ;
From the Departments of Medicine (M.M.W., L.Y., Y.T., X.W., X.W., L.W.C., A.J.L., L.G.F., A.P.B., S.G.Y.) and Human Genetics (M.M.W., A.J.L., S.G.Y.), University of California, Los Angeles; and the Department of Poultry Science (R.L.W.), Texas A&M University, College Station.
* To whom correspondence should be addressed. E-mail: sgyoung{at}mednet.ucla.edu.
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.
Key words: lipoprotein lipase • chylomicronemia • lipolysis • GPIHBP1