Macrophage-expressed group IIA secretory phospholipase A2 increases atherosclerotic lesion formation in LDL receptor-deficient mice.
OBJECTIVE
Transgenic mice expressing human group IIA secretory phospholipase A(2) (group IIA sPLA(2)) 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 sPLA(2). This study tested whether macrophage-expressed sPLA(2) contributes to atherogenesis.


RESULTS
Bone marrow cells from either sPLA(2) 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 sPLA(2) 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 mm(2) versus 0.2+/-0.04 mm(2); P<0.05).


CONCLUSIONS
Group IIA sPLA(2) can contribute to atherosclerotic lesion development through a mechanism that is independent of systemic lipoprotein metabolism.
Webb
Nancy R
NR
Department of Internal Medicine, University of Kentucky Medical Center MN520, 800 Rose St, Lexington, KY 40536-0084, USA. nrwebb1@uky.edu
Bostrom
Meredith A
MA
Szilvassy
Stephen J
SJ
van der Westhuyzen
Deneys R
DR
Daugherty
Alan
A
de Beer
Frederick C
FC
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D001854:Bone Marrow Cells / Q000201:enzymology; D016026:Bone Marrow Transplantation; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D004036:Diet, Atherogenic; D004041:Dietary Fats; D054501:Group II Phospholipases A2; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008074:Lipoproteins / Q000097:blood; D017737:Macrophages, Peritoneal / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010741:Phospholipases A / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D054467:Phospholipases A2; D011973:Receptors, LDL / Q000172:deficiency*
D004041:Dietary Fats; D008074:Lipoproteins; D011973:Receptors, LDL; D002784:Cholesterol; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2