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通过保持动脉完整性来限制血管CXCR4:来自小鼠和人类研究的证据
Yvonne Döring, Heidi Noels1, Emiel P C van der Vorst
1From Institute for Cardiovascular Prevention (IPEK), LMU Munich, Germany (Y.D., E.P.C.v.d.V., C.N., V.E., M.D., M.M., Y.J., K.B., R.T.A.M., C.R., O.S., E.T., C.W.); Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Germany (H.N., L.P., W.T.); Institute for Cardiovascular Physiology, Vascular Research Centre, Goethe University, Frankfurt am Main, Germany (K.S., R.P.B.); Division of Nephrology and Immunology, RWTH Aachen University Hospital, Germany (B.M.K., P.B.); Cardiovascular Research Institute Maastricht (CARIM), Department of Biochemistry, Maastricht University, the Netherlands (R.T.A.M., R.v.G., T.M.H., C.W.); Academic Medical Center, Department of Pathology and Department of Medical Biochemistry, Amsterdam University, the Netherlands (P.J.H.K., A.v.D.W., E.T.); Department of Vascular and Endovascular Surgery, LMU Munich, Germany (G.G.); DZHK (German Centre for Cardiovascular Research), partner site Frankfurt am Main, Germany (R.P.B.); DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Germany (O.S., C.W.); Department of Physiology and Pharmacology, Karolinksa Institutet, Stockholm, Sweden (O.S.); Max-Plank-Institute for Molecular Biomedicine, Münster, Germany (D.V.); Institute for Laboratory Medicine, LMU Munich, Germany (D.T., L.M.H.); and Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (D.J.R., D.S.).
血管CXCR4通过保持动脉完整性和内皮屏障功能来限制动脉样硬化. CXCR4 的基因变异与冠状动脉疾病风险有关,这表明其具有治疗潜力.
科学领域:
- 心血管生物学
- 分子医学
- 免疫学
背景情况:
- 在CXCL12/CXCR4轴调节细胞平衡和贩运.
- 之前的研究暗示CXCL12/CXCR4通过药理手段具有动脉保护作用.
- 在血管细胞和动脉样硬化机制中CXCR4的具体作用尚不清楚.
研究的目的:
- 研究血管CXCR4在动脉样硬化和斑块组成中的作用.
- 阐明CXCR4在动脉壁中的基本机制.
- 评估CXCR4位点的遗传变异与冠心病风险的关联.
主要方法:
- 在动脉硬化模型中生成内皮细胞或光滑肌细胞 (SMC) 特定的CXCR4缺乏的小鼠.
- 评估了内皮通透性,白细胞粘附性,Akt/WNT/β-catenin信号传递,VE-cadherin功能,血管度和SMC表型.
- 分析了CXCR4变异与冠状动脉疾病的遗传关联以及人类斑块中的CXCR4表达.
主要成果:
- 细胞特异性CXCR4缺乏在内皮细胞或SMCs加剧动脉样硬化.
- 保持CXCR4信号内皮屏障功能和SMC收缩表型.
- 基因分析将CXCR4位点变异 (rs2322864 C- 基因) 与冠状动脉疾病风险的增加和人类斑块中CXCR4表达的减少联系在一起.
结论:
- 通过保持动脉完整性和内皮功能,血管CXCR4对于限制动脉样硬化至关重要.
- 此外,CXCR4还保持了正常的SMC表型和血管反应.
- 针对血管CXCR4可能为动脉样硬化提供新的治疗策略.
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