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 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.