Abstract

Introduction: Primary intracerebral hemorrhage (ICH) stroke is a serious complication of uncontrolled hypertension. Recent clinical studies have shown that circulating microparticles (MPs) from endothelia (EMPs), platelets (PMPs) and endothelial progenitor cells (EPC-MPs) are potential biomarkers for cardiovascular diseases. However, the role of circulating MPs in ICH stroke is unknown. Methods and Results: The human renin and angiotensinogen transgenic (R+A+) and the control (R−A−) mice (male, 8 –10 weeks) were fed with normal diet or high salt diet (8% NaCl, HSD) plus nitric oxide synthase inhibitor L-NAME (120 mg/kg/day) in drinking water for two weeks. Mean arterial pressure (MAP) was measured using telemetric probes. Circulating MPs were identified by membrane markers, CD62E (for EMPs), CD62P (for PMPs), and CD34 and VEGFR2 (for EPC-MPs) using flow cytometry. The severity of ICH was determined by histological analysis of total bleeding area. The lumen/wall in the middle cerebral artery (MCA) was histologically measured. Results (Table and Figure ) showed: The R+A+ mice were hypertensive and had higher basal level of circulating PMPs and EMPs with no difference in EPC-MPs; After fed with HSD and L-NAME, R+A+ mice had severe hypertension and 50% of them developed ISH stroke within two weeks; There was a further increase of EMPs and a decrease of EPC-MPs in R+A+ mice with ICH stroke; There were strong correlations of EMPs (r=0.44~0.61) and EPC-MPs (r=−0.52~0.78) with MAP, MCA lumen/wall and total area of bleeding sites. Conclusion: Circulating EPC-MPs and EMPs could serve as useful biomarkers for uncontrolled hypertension, MCA remodeling and ICH stroke. Table. Blood pressure, circulating MPs and MCA lumen/wall in R+A+ and R−A− mice fed with normal diet or HSD and L-NAME for two weeks Fig. Hemorrhages in the brain (A, D: brainstem: B, E: cerebellum; C,F: basal ganglia) and MCA remodeling, A–C; R+A+ mice fed with HSD+L-NAME; D–F: R−A− mice fed with HSD+L-NAME; G: R−A− mice fed with normal diet, H: R−A− mice fed with HSD+L-NAME; I: R+A+ mice fed with HSD+L-NAME

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