Macrophage-expressed group IIA secretory phospholipase A2 increases atherosclerotic lesion formation in LDL receptor-deficient mice

Nancy R. Webb, Meredith A. Bostrom, Stephen J. Szilvassy, Deneys R. Van der Westhuyzen, Alan Daugherty, Frederick C. De Beer

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Objective - Transgenic mice expressing human group IIA secretory phospholipase A2 (group IIA sPLA2) spontaneously develop atherosclerotic lesions. The mechanism for this proatherogenic effect is likely multifactorial, because HDL-cholesterol is significantly lower and LDL/VLDL cholesterol is slightly higher in transgenic mice compared with nontransgenic littermates. In the present study, we show for the first time that elicited peritoneal macrophages from transgenic mice express human group IIA sPLA2. This study tested whether macrophage-expressed sPLA2 contributes to atherogenesis. Methods and Results - Bone marrow cells from either sPLA2 transgenic mice or control C57BL/6 mice were transplanted into LDL receptor-deficient mice. After hematopoietic engraftment, animals were fed a diet enriched with saturated fat and cholesterol for 12 weeks. Despite a lack of effect on serum lipoprotein concentrations, the presence of bone marrow-derived cells expressing human group IIA sPLA2 resulted in a significant increase in the extent of atherosclerosis in the aortic arch (12.8±1.4% versus 7.4±0.9%; P<0.005) and aortic sinus (0.3±0.03 mm2 versus 0.2±0.04 mm2; P<0.05). Conclusions - Group IIA sPLA2 can contribute to atherosclerotic lesion development through a mechanism that is independent of systemic lipoprotein metabolism.

Original languageEnglish
Pages (from-to)263-268
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number2
StatePublished - Feb 1 2003


  • Atherosclerosis
  • Bone marrow transplant
  • Macrophages
  • Transgenic mice group IIA secretory phospholipase A

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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