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.
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.
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.