CD36/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury.
Hyperlipidemia with accompanying increase in peripheral inflammation is a risk factor for stroke. The effect of excess lipids on stroke-induced injury and the mechanism by which lipid-mediated inflammatory responses contribute to stroke are not known. We investigated these uncertainties by subjecting normal and hyperlipidemic mice to transient middle cerebral artery occlusion, followed by measurement of stroke severity and inflammatory response. Infarct size, swelling, and lipid contents were significantly increased in the high-fat fed ApoE knock-out mice, as was the expression of the inflammatory mediators CD36 and monocyte chemoattractant protein 1 (MCP-1) in the brain and periphery. Furthermore, the hyperlipidemic mice exhibited numerous foam cells, a probable cause of increased swelling and postischemic inflammation, in the peri-infarct area. Genetic deletion of cd36 in the hyperlipidemic condition reduced proinflammatory chemokine/receptor and cytokines (MCP-1, CC chemokine receptor 2, and interleukins 1beta and 6), in the brain 6 h after ischemia. The reduced proinflammatory response also resulted in smaller ischemic injury, less swelling, and fewer foam cells at 3 d after ischemia. The results show that hyperlipidemia-induced inflammation is a negative factor for stroke outcomes and indicate that downregulating CD36 may be an effective therapeutic strategy for reducing the impact of stroke in hyperlipidemic subjects.
Kim
Eunhee
E
Burke Medical Research Institute, White Plains, New York 10605, USA.
Tolhurst
Aaron T
AT
Qin
Lu Ye
LY
Chen
Xin-Yuan
XY
Febbraio
Maria
M
Cho
Sunghee
S
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D001835:Body Weight / Q000502:physiology; D001929:Brain Edema / Q000209:etiology; D020520:Brain Infarction / Q000209:etiology* / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006949:Hyperlipidemias / Q000150:complications*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism
C487540:ABCG1 protein, mouse; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D018955:CD36 Antigens; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D008074:Lipoproteins; D054390:Receptors, CCR2; D002784:Cholesterol