The capacity of group V sPLA2 to increase atherogenicity of ApoE-/- and LDLR-/- mouse LDL in vitro predicts its atherogenic role in vivo.
The capacity of group V sPLA2 to increase atherogenicity of ApoE-/- and LDLR-/- mouse LDL in vitro predicts its atherogenic role in vivo.
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DOI：
10.1161/atvbaha.108.183038
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
Webb NR
中科院分区：
文献类型：
--
作者：
Boyanovsky B;Zack M;Forrest K;Webb NR
In vitro data indicate that human LDL modified by Group V secretory phospholipase A2 (GV sPLA2) is pro-atherogenic. 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. LDL (d = 1.019-1.063) 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 pre-requisite 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. 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.
