Atheroprotective effect of human apolipoprotein A5 in a mouse model of mixed dyslipidemia.
Hypertriglyceridemia is an independent risk factor for coronary artery disease. Because apolipoprotein (Apo)A5 regulates plasma triglyceride levels, we investigated the impact of human (h)ApoA5 on atherogenesis. The influence of hApoA5 transgenic expression was studied in the ApoE2 knock-in mouse model of mixed dyslipidemia. Our results demonstrate that hApoA5 lowers plasma triglyceride levels in Western diet-fed ApoE2 knock-in mice. Moreover, atherosclerotic lesion development was significantly decreased in the hApoA5 transgenic mice. Finally, pharmacologic activation of hApoA5 expression by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate resulted in an enhanced atheroprotection. These results identify an atheroprotective role of hApoA5 in a mouse model of mixed dyslipidemia.
Mansouri
Roxane M
RM
Inserm, U545, Institut Pasteur de Lille, Lille F-59019, France.
Baugé
Eric
E
Gervois
Philippe
P
Fruchart-Najib
Jamila
J
Fiévet
Catherine
C
Staels
Bart
B
Fruchart
Jean-Charles
JC
D000821:Animal Feed; D000818:Animals; D000072040:Apolipoprotein A-V; D053329:Apolipoprotein E2 / Q000097:blood / Q000235:genetics; D001054:Apolipoproteins A / Q000235:genetics* / Q000378:metabolism*; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014280:Triglycerides / Q000097:blood*
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053329:Apolipoprotein E2; D001054:Apolipoproteins A; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol; D011345:Fenofibrate