Possible Role of Circulating Cellular Microparticles in Progressive Hypertension and Middle Cerebral Artery Remodeling
Circulating cellular microparticles (MPs) are potential biomarkers for cardiovascular diseases and are also suggested to be involved in the pathogenesis of hypertension and stroke. We assessed the hypothesis that circulating MPs could have implications in influencing mean arterial pressure (MAP) and middle cerebral artery (MCA) remodeling via changes in their levels and contents. Male C57BL/6 mice were fed with normal diet (control) or induced to progressive hypertension by infusion with angiotensin II (ANG II, 42µg/kg/h, osmotic minipump) and fed with high-salt diet (HSD, 8% NaCl) plus L-NAME (120 mg/kg/day, in drinking water) for 2 (for MPs donor) and 4 weeks (for MP infusion study). Circulating MPs isolated from control (cMPs) or hypertensive (hMPs) mice were isolated as we previously described (Chen, et al, AJP, 2011). The levels of circulating endothelial MPs (EMPs) and endothelial progenitor cells-MPs (EPC-MPs) were analyzed using flow cytometry by staining with CD144 (EMPs), CD34 and VEGFR2 (EPC-MPs), respectively. The mRNA levels of CXCR4, endothelial nitric oxide synthase (eNOS), NOX2 and tumor necrosis factor-alpha (TNF-a) in circulating MPs were determined by quantitative real-time RT-PCR. In separate experiment, control or hypertensive mice were treated with infusion of cMPs or hMPs (1x105/100µl) via tail vein once per week for two continuous weeks, and sacrificed at the end of experiment (week four). MAP was measured using radiotelemetric probe. The lumen/wall in the MCA was determined by Hematoxylin and Eosin staining. Results showed (table): 1) Mice infused with ANG II and fed with HSD and L-NAME showed progressive hypertension and MCA remodeling. 2) The levels of EMP and EPC-MPs were significantly increased in hypertensive mice. 3) hMPs carried less CXCR4 and eNOS, and higher NOX2 and TNF-a mRNAs when compared with cMPs. 4) Infusion of hMPs increased MAP and MCA remodeling in hypertensive mice, but only induced MCA remodeling in control mice. 5) cMPs decreased MAP and MCA in hypertensive mice, but had no effect on MCA remodeling and MAP in control mice. In conclusion, circulating MPs could be served as biomarkers and used for developing therapeutic avenues for progressive hypertensive and MCA remodeling.
& Chen, Y.
(2012). Possible Role of Circulating Cellular Microparticles in Progressive Hypertension and Middle Cerebral Artery Remodeling. International Stroke Conference.