TY - JOUR
T1 - Group V sPLA2 Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation
AU - Wooton-Kee, C. Ruth
AU - Boyanovsky, Boris B.
AU - Nasser, Munira S.
AU - De Villiers, Willem J.S.
AU - Webb, Nancy R.
PY - 2004/4
Y1 - 2004/4
N2 - Objectives-Secretory phospholipase A2 (sPLA2) enzymes hydrolyze the sn-2 fatty acyl ester bond of phospholipids to produce a free fatty acid and a lysophospholid. Group V sPLA2 is expressed in cultured macrophage cells and has high affinity for phosphatidyl choline-containing substrates. The present study assesses the presence of group V sPLA2 in human and mouse atherosclerotic lesions and its activity toward low-density lipoprotein (LDL) particles. Methods and Results-Group V sPLA2 was detected in human and mouse atherosclerotic lesions by immunohistochemical staining. Electron microscopic analysis showed that mouse group V sPLA2-modified LDL is significantly smaller (mean diameter±SEM=25.3±0.25 nm) than native LDL (mean diameter±SEM=27.7±0.29 nm). Hydrolysis by group V sPLA 2 induced spontaneous particle aggregation; the extent of aggregation was directly proportional to the degree of LDL hydrolysis. Group V sPLA2 modification of LDL led to enhanced lipid accumulation in cultured mouse peritoneal macrophage cells. Conclusions-Group V sPLA 2 may play an important role in promoting atherosclerotic lesion development by modifying LDL particles in the arterial wall, thereby enhancing particle aggregation, retention, and macrophage uptake.
AB - Objectives-Secretory phospholipase A2 (sPLA2) enzymes hydrolyze the sn-2 fatty acyl ester bond of phospholipids to produce a free fatty acid and a lysophospholid. Group V sPLA2 is expressed in cultured macrophage cells and has high affinity for phosphatidyl choline-containing substrates. The present study assesses the presence of group V sPLA2 in human and mouse atherosclerotic lesions and its activity toward low-density lipoprotein (LDL) particles. Methods and Results-Group V sPLA2 was detected in human and mouse atherosclerotic lesions by immunohistochemical staining. Electron microscopic analysis showed that mouse group V sPLA2-modified LDL is significantly smaller (mean diameter±SEM=25.3±0.25 nm) than native LDL (mean diameter±SEM=27.7±0.29 nm). Hydrolysis by group V sPLA 2 induced spontaneous particle aggregation; the extent of aggregation was directly proportional to the degree of LDL hydrolysis. Group V sPLA2 modification of LDL led to enhanced lipid accumulation in cultured mouse peritoneal macrophage cells. Conclusions-Group V sPLA 2 may play an important role in promoting atherosclerotic lesion development by modifying LDL particles in the arterial wall, thereby enhancing particle aggregation, retention, and macrophage uptake.
KW - Atherosclerosis
KW - Group V secretory phospholipase A
KW - LDL aggregation
KW - Macrophages
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U2 - 10.1161/01.ATV.0000122363.02961.c1
DO - 10.1161/01.ATV.0000122363.02961.c1
M3 - Article
C2 - 14962950
AN - SCOPUS:1842475761
SN - 1079-5642
VL - 24
SP - 762
EP - 767
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 4
ER -