Abstract 3535: CD36 Impacts Stroke Injury In Hyperlipidemia Through MCP-1/CCR2 Axis.
Hyperlipidemia increases ischemic injury. The exacerbation is associated with elevated expression of CD36, a class B scavenger receptor, in peripheral monocytes/macrophages as well as ischemic brain (Kim et al., 2008). This study investigates whether and how peripheral and brain CD36 contribute to stroke-induced brain injury in hyperlipidemia. Bone marrow cells (BM) were exchanged between CD36-expressing (AKO) and CD36-deficient (DKO) mice. The experimental mice were fed a high fat diet for 11 weeks and then subjected to transient ischemic stroke by middle cerebral artery occlusion. Ischemic outcome, MCP-1, CCR2 in the brain, and plasma MCP-1 levels were determined at 3 days post-ischemia. Compared to AKO mice received AKOBM (control transplant), the AKO mice received DKOBM resulted in 30% reduction in infarct volume (IV) (n=12-14, p<0.05, Fig. 1 left), 27% in MCP-1 (p<0.05) and 35% CCR2 (p<0.05) mRNA levels. In contrast, DKO mice received AKOBM did not increase IV (Fig. 1 right), MCP-1 or CCR2 mRNA levels compared to DKO mice received DKOBM (n=11-15, ns). Correlation analyses of MCP-1 vs IV or CCR2 vs IV showed significant reductions in slope elevations in DKO mice compared to AKO (MCP-1 vs IV, p<0.05; CCR2 vs IV, p<0.01, n=23-25/group). In spite of blunted MCP-1 expression in ischemic brain, plasma MCP-1 levels were significantly higher in DKO mice (DKO, 441.5±33.6pg/ml vs AKO, 235.8±15.9pg/ml, n=25, p<0.001). We further addressed in vitro the importance of CD36 in splenocytes for CCR2 expression. In a given AKO or DKO serum, CCR2 expression was higher in AKO splenocytes compared to DKO splenocytes (Fig. 2). This study demonstrates several findings; i) peripheral CD36 contributes ischemic injury in hyperlipidemia; ii) brain (host) CD36 is additionally required for the peripheral CD36 effect take place iii) DKO host displays reduced MCP-1/CCR2 expression in the post-ischemic brain but higher plasma MCP-1 levels iv) CD36 regulates CCR2 expression in splenocytes. The findings suggest that host and peripheral CD36 synergistically regulates immune cells trafficking through modulating MCP-1/CCR2 axis. Thus, targeting CD36 may serve as a novel neuro-immune strategy to achieve neuroprotection from stroke-induced acute brain injury in hyperlipidemia.
- © 2012 by American Heart Association, Inc.