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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1809.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Macrophage-Specific Expression of Human Lipoprotein Lipase Accelerates Atherosclerosis in Transgenic Apolipoprotein E Knockout Mice but Not in C57BL/6 Mice

Katina Wilson; Glenna L. Fry; David A. Chappell; Curt D. Sigmund; Jheem D. Medh

From the Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa.

Consulting editor for this article was Alan M. Fogelman, MD, Professor of Medicine and Executive Chair, Departments of Medicine and Cardiology, UCLA School of Medicine, Los Angeles, Calif.Reprint requests to Jheem D. Medh, Department of Chemistry, California State University, 18111 Nordhoff St, Northridge, CA 91330-8262. E-mail jheem.medh{at}csun.edu

Abstract—— Transgenic mice with macrophage-specific expression of human (hu) lipoprotein lipase (LPL) were generated to determine the contribution of macrophage LPL to atherogenesis. Macrophage specificity was accomplished with the scavenger receptor A promoter. Complete characterization demonstrated that macrophages from these mice expressed huLPL mRNA and secreted enzymatically active huLPL protein. Expression of huLPL was macrophage specific, because total RNA isolated from heart, thymus, lung, liver, muscle, and adipose tissues was devoid of huLPL mRNA. Macrophage-specific expression of huLPL did not exacerbate lesions in aortas of C57BL/6 mice even after 32 weeks on an atherosclerotic diet. However, when expressed in apolipoprotein E knockout background, the extent of occlusion in the aortic sinus region of male huLPL+ mice increased 51% (n=9 to 11, P<0.002) compared with huLPL- mice after they had been fed a Western diet for 8 weeks. The proatherogenic effect of macrophage LPL was confirmed in serial sections of the aorta obtained after mice had been fed a Western diet for 3 weeks. By immunohistochemical analysis, huLPL protein was detected in the lesions of huLPL+ mice but not in huLPL- mice. Our results establish that macrophage LPL accelerates atherosclerosis in male apolipoprotein E knockout mice.

Key Words: lipoprotein lipase • macrophages • atherosclerosis • apoE knockout mice • transgenic mice

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