Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice.
We examined whether the putative anti-atherogenic enzymes LCAT, paraoxonase (PON), and platelet-activating factor acetylhydrolase (PAF-AH) are impaired in 8 week old atherosclerosis susceptible apolipoprotein E (apoE)(-/-) and LDL receptor (LDLr)(-/-) mice and whether plasma concentrations of bioactive oxidized phospholipids accumulate in plasma. ApoE(-/-) mice had reduced (28%) LCAT activity and elevated lysophosphatidylcholine and bioactive oxidized phospholipids (1-palmitoyl-2-oxovaleryl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine) compared with controls on the chow diet. Elevated oxidized phospholipids and reduced LCAT activity may, in part, contribute to spontaneous lesions in these mice on a chow diet. A Western diet decreased LCAT activity further (50% of controls) and PON activity was decreased 38%. The LDLr(-/-) mice showed normal LCAT activity on chow diet and little accumulation of oxidized phospholipids. On a Western diet, LDLr(-/-) mice had reduced LCAT activity (21%), but no change in PON activity. All genotypes had reduced PAF-AH activity on the Western diet. ApoE(-/-) and LDLr(-/-) mice, but not controls, had elevated plasma bioactive oxidized phospholipids on the Western diet. We conclude that impairment of LCAT activity and accumulation of oxidized phospholipids are part of an early atherogenic phenotype in these models.
Forte
Trudy M
TM
Life Sciences Division MS 1-222, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. tmforte@lbl.gov
Subbanagounder
Ganesamoorthy
G
Berliner
Judith A
JA
Blanche
Patricia J
PJ
Clermont
Anne O
AO
Jia
Zhen
Z
Oda
Michael N
MN
Krauss
Ronald M
RM
Bielicki
John K
JK
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D043303:Aryldialkylphosphatase; D004032:Diet; D004950:Esterases / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*
D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D008055:Lipids; D008074:Lipoproteins; D010743:Phospholipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D004950:Esterases; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase