Abstract P269: Chronic Cerebral Ischemic Injury Worsens Vascular Dysfunction

Abstract

Introduction: Distant organ dysfunction has been highlighted whereby acute or chronic damage in one organ may induce acute or chronic dysfunctions of the other organs such as cardiorenal syndrome. Vascular remodeling is an important process in various vascular diseases. However, the relationship cerebral ischemic damage and peripheral vascular disorder is still unclear. Therefore, we have investigated the possible pathophysiological interactions between brain ischemia and vascular remodeling. Methods: Eight-week-old male C57BL/6 mice underwent permanent cerebral brain ischemia by permanent occlusion of the left middle cerebral artery occlusion (MCAO) by electrocoagulation using a subtemporal approach. Four weeks after MCAO, vascular injury was induced by polyethylene cuff placement on the femoral artery. Neointima formation was determined 14 days after cuff placement by evaluating intima/media ratio. Macrophage fractions in spleen two weeks after MCAO were examined and M1 and M2-polarized macrophages were separated by flow cytometry and analyzed. Results: Body weight after MCAO and cuff placement did not differ among all groups. Cerebral ischemia did not influence the intima/media ratio 6 weeks after MCAO (MCAO-Cuff (-), 0.123) compared with sham-operated mice (sham-Cuff (-), 0.120). Neointima formation in the injured artery was significantly increased 2 weeks after cuff placement (sham-Cuff (+), 0.258). Interestingly, the neointima formation 2 weeks after cuff placement was more marked in MCAO-operated mice (MCAO-Cuff (+), 0.369) compared with sham-Cuff (+). Next, we examined the macrophage fractions in spleen 2 weeks after MCAO. The macrophage fraction in SVF evaluated by F4/80 staining did not differ between sham- (7.5%) and MCAO-operated (7.6%) mice. There was no significant difference in M1 and M2 fraction with/without MCAO. Conclusion: These results suggest that cerebral ischemic injury aggravate peripheral vascular disorders, and we are addressing the possible roles of renin-angiotensin system and oxidative stress etc. involved in these interesting results, which could provide us with the discovery of new pathological mechanisms concerning the distant organ dysfunctions between brain and peripheral vasculature.