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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:532.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

The Capacity of Group V sPLA₂ to Increase Atherogenicity of ApoE^–/– and LDLR^–/– Mouse LDL In Vitro Predicts its Atherogenic Role In Vivo

Boris Boyanovsky; Melissa Zack; Kathy Forrest; Nancy R. Webb

From the Department of Internal Medicine and Cardiovascular Research Center (B.B., K.F., N.R.W.), and the Graduate Center for Nutritional Sciences (M.Z., N.R.W.), University of Kentucky Medical Center, Lexington.

Correspondence to Nancy R. Webb, 900 South Limestone Street, Rm 535, University of Kentucky, Lexington, KY 40536-0200. E-mail nrwebb1{at}email.uky.edu

Objective— In vitro data indicate that human LDL modified by Group V secretory phospholipase A₂ (GV sPLA₂) is proatherogenic. Consistent with this, gain and loss of function studies demonstrated that GV sPLA₂ promotes atherosclerosis in LDLR^–/– mice. The current study investigates whether GV sPLA₂ promotes atherosclerotic processes in apoE^–/– mice.

Methods and Results— LDL (d=1.019 to 1.063) from apoE^–/– and LDLR^–/– mice fed chow or Western diet were hydrolyzed by GV sPLA₂. Phosphatidylcholine on LDL from LDLR^–/– mice fed either a chow or Western diet was hydrolyzed to a greater extent (61.1±0.4% and 45.3±4.6%) than the corresponding fractions from apoE^–/– mice (41.7±3.6% and 39.4±1.2%). ApoE^–/– LDL induced macrophage foam cell formation in vitro without modification by GV sPLA₂, whereas hydrolysis of LDLR^–/– LDL was a prerequisite for foam cell formation. In contrast to findings in LDLR^–/– mice, GV sPLA₂ deficiency did not significantly reduce atherosclerosis in apoE^–/– mice, although collagen content was significantly reduced in lesions of apoE^–/– mice lacking GV sPLA₂.

Conclusions— The ability of GV sPLA₂ to promote atherosclerotic lipid deposition in apoE^–/– and LDLR^–/– mice may be related to its ability to increase the atherogenic potential of LDL from these mice as assessed in vitro.

Key Words: sphingomyelin • foam cells • cholesterol ester • atherosclerosis