title: Deficiency in sPLA(2) does not affect HDL levels or atherosclerosis in mice.
abstract: Secretory non-pancreatic phospholipase A(2) (sPLA(2)) has been implicated in inflammation and has been found in human atherosclerotic lesions. To test the effect of sPLA(2) deficiency on atherosclerosis, C57BL/Ks mice (apoE(+/+) and PLA(2)(++) were bred with C57BL/6 apoE knockout mice which are sPLA(2)(--) due to a spontaneous mutation. Sibling pairs of mice (apoE(--)/sPLA(2)(++) and apoE(--)/sPLA(2)(--)) on high fat Western diets were dissected at 22 weeks. In vitro enzyme assays confirmed higher serum sPLA(2) activity in the sPLA(2)(++) compared to sPLA(2)(--) for both sexes, while sPLA(2)(--) males had slightly higher serum cholesterol and phospholipids. Analysis of lipoprotein profiles by FPLC showed no effect of sPLA(2) genotype on any measured parameters. Atherosclerosis was quantitated by assaying cholesterol in aortic extracts. Male sPLA(2) trended slightly higher than sPLA(2)(++) with no statistical significance. Female sPLA(2)(++) and sPLA(2)(--) mice showed no significant differences in any of the measured parameters. These results suggest that the endogenous mouse sPLA(2) gene does not significantly affect HDL or atherosclerosis in mice.
authors.affiliation: Merck Research Laboratories, 126 E. Lincoln Avenue, RY80W-250 Rahway, NJ 07065-4607, USA. charlotte_burton@merck.com
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Burton
authors.forename: Sushma
authors.initials: S
authors.lastname: Patel
authors.forename: Steven
authors.initials: S
authors.lastname: Mundt
authors.forename: Heide
authors.initials: H
authors.lastname: Hassing
authors.forename: Donghui
authors.initials: D
authors.lastname: Zhang
authors.forename: Anne
authors.initials: A
authors.lastname: Hermanowski-Vosatka
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Wright
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Detmers
authors.forename: Carl P
authors.initials: CP
authors.lastname: Sparrow
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D001161:Arteriosclerosis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D054501:Group II Phospholipases A2; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010741:Phospholipases A / Q000172:deficiency* / Q000378:metabolism; D012737:Sex Factors
chemical_list: D001057:Apolipoproteins E; D004041:Dietary Fats; D008055:Lipids; D008075:Lipoproteins, HDL; D010741:Phospholipases A; D054501:Group II Phospholipases A2