The capacity of Group V sPLA2 to increase atherogenicity of apoE-/- and LDLR-/- mouse LDL in vitro predicts its atherogenic role in vivo

Objective— In vitro data indicate that human LDL modified by Group V secretory phospholipase A 2 (GV sPLA 2 ) is proatherogenic. Consistent with this, gain and loss of function studies demonstrated that GV sPLA 2 promotes atherosclerosis in LDLR −/− mice. The current study investigates whether GV sPLA 2 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 sPLA 2 . 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 sPLA 2 , whereas hydrolysis of LDLR −/− LDL was a prerequisite for foam cell formation. In contrast to findings in LDLR −/− mice, GV sPLA 2 deficiency did not significantly reduce atherosclerosis in apoE −/− mice, although collagen content was significantly reduced in lesions of apoE −/− mice lacking GV sPLA 2 . Conclusions— The ability of GV sPLA 2 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.