Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo

Vladimir R. Babaev, Sergio Fazio, Linda A. Gleaves, Kathy J. Carter, Clay F. Semenkovich, MacRae F. Linton

Research output: Contribution to journalArticle

175 Citations (Scopus)

Abstract

Expression of lipoprotein lipase (LPL) by the macrophage has been proposed to promote foam cell formation and atherosclerosis, primarily on the basis of in vitro studies. LPL-deficient mice might provide a model for testing the role of LPL secretion by the macrophage in an in vivo system. Unfortunately, homozygous deficiency of LPL in the mouse is lethal shortly after birth. Because the fetal live r is the major site of hematopoiesis in the developing fetus, transplantation of C57BL/6 mice with LPL(-/-) fetal liver cells (FLCs) was used to investigate the physiologic role of macrophage LPL expression in vivo. Thirty-four female C57BL/6 mice were lethally irradiated and reconstituted with FLCs from day 14 LPL(+/+) LPL(+/-), and LPL(-/-) donors. No significant differences were detected in plasma levels of post-heparin LPL activity or in serum cholesterol or triglyceride levels between the 3 groups on either a chow diet or an atherogenic diet. After 19 weeks on the atherogenic diet, aortae were collected for quantitative analysis of the extent of aortic atherosclerosis. LPL expression was detected by immunocytochemistry and in situ hybridization in macrophages of aortic atherosclerotic lesions of LPL(+/+)→C57BL/6 and LPL(+/-)→C57BL/6 mice, but not in LPL(-/-)→C57BL/6 mice, whereas myocardial cells expressed LPL in all groups. The mean aortic lesion area was reduced by 55% in LPL(-/-)→C57BL/6 mice compared with LPL(+/+)→C57BL/6 mice and by 45% compared with LPL(+/- )→C57BL/6 mice, respectively. These data demonstrate in vivo that LPL expression by macrophages in the artery wall promotes foam cell formation and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1697-1705
Number of pages9
JournalJournal of Clinical Investigation
Volume103
Issue number12
StatePublished - Jun 1999
Externally publishedYes

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Foam Cells
Lipoprotein Lipase
Atherosclerosis
Macrophages
Inbred C57BL Mouse
Atherogenic Diet
Hyperlipoproteinemia Type I

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Babaev, V. R., Fazio, S., Gleaves, L. A., Carter, K. J., Semenkovich, C. F., & Linton, M. F. (1999). Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. Journal of Clinical Investigation, 103(12), 1697-1705.

Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. / Babaev, Vladimir R.; Fazio, Sergio; Gleaves, Linda A.; Carter, Kathy J.; Semenkovich, Clay F.; Linton, MacRae F.

In: Journal of Clinical Investigation, Vol. 103, No. 12, 06.1999, p. 1697-1705.

Research output: Contribution to journalArticle

Babaev, VR, Fazio, S, Gleaves, LA, Carter, KJ, Semenkovich, CF & Linton, MF 1999, 'Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo', Journal of Clinical Investigation, vol. 103, no. 12, pp. 1697-1705.
Babaev VR, Fazio S, Gleaves LA, Carter KJ, Semenkovich CF, Linton MF. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. Journal of Clinical Investigation. 1999 Jun;103(12):1697-1705.
Babaev, Vladimir R. ; Fazio, Sergio ; Gleaves, Linda A. ; Carter, Kathy J. ; Semenkovich, Clay F. ; Linton, MacRae F. / Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 12. pp. 1697-1705.
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