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. (Arterioscler Thromb Vasc Biol. 2009; 29: 532-538.)