Faculty Collaboration Database

Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein e knockout mice but not in C57BL/6 mice. Arterioscler Thromb Vasc Biol 2001 Nov;21(11):1809-15

Date

11/10/2001

Pubmed ID

11701470

Pubmed Central ID

PMC2768479

DOI

10.1161/hq1101.097805

Scopus ID

2-s2.0-0035571614 (requires institutional sign-in at Scopus site)   58 Citations

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.

Author List

Wilson K, Fry GL, Chappell DA, Sigmund CD, Medh JD

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Apolipoproteins E
Arteriosclerosis
Cells, Cultured
Female
Humans
Lipids
Lipoprotein Lipase
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
RNA, Messenger
Tissue Distribution
Transcription, Genetic