SDF-1α/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells
SDF-1α/CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells
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DOI：
10.1161/01.res.0000162100.52009.38
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发表时间：
2005-04-15
影响因子：
20.1
通讯作者：
Weber, C
中科院分区：
文献类型：
--
作者：
Zernecke, A;Schober, A;Weber, C
最近的证据推断平滑肌细胞（SMC）祖细胞和基质细胞衍生因子（SDF）-1 α对动脉损伤后新生内膜形成的贡献。在用LacZ（+）或CXCR 4（-/-）BM或拮抗剂的慢病毒转移重新填充的载脂蛋白E缺陷小鼠中，斑块面积和SMC含量的抑制揭示了局部SDF-1 α及其受体CXCR 4通过募集BM衍生的SMC祖细胞在新生内膜增生中的重要参与。动脉损伤后，中层SMC中SDF-1 α的表达在凋亡之前，并通过阻断caspase依赖性凋亡来抑制。SDF-1 α在损伤部位与血小板结合，触发CXCR 4和P-选择素依赖性的祖细胞在损伤动脉或基质粘附血小板上的阻滞，优先动员和招募c-kit（-）/血小板衍生生长因子受体（PDGFR）-β（+）/谱系（-）/sca-1（+）祖细胞用于新生内膜SMC，而不需要它们的分化。因此，SDF-1 α/CXCR 4轴是血管重塑的关键，通过招募SMC祖细胞的一个子集来响应细胞凋亡并与血小板一致，体现了其对组织修复的重要性，并确定了限制病变发展的主要靶点。
Recent evidence infers a contribution of smooth muscle cell (SMC) progenitors and stromal cell-derived factor (SDF)-1 alpha to neointima formation after arterial injury. Inhibition of plaque area and SMC content in apolipoprotein E-deficient mice repopulated with LacZ(+) or CXCR4(-/-) BM or lentiviral transfer of an antagonist reveals a crucial involvement of local SDF-1 alpha and its receptor CXCR4 in neointimal hyperplasia via recruitment of BM-derived SMC progenitors. After arterial injury, SDF-1 alpha expression in medial SMCs is preceded by apoptosis and inhibited by blocking caspase-dependent apoptosis. SDF-1 alpha binds to platelets at the site of injury, triggers CXCR4- and P-selectin-dependent arrest of progenitor cells on injured arteries or matrix-adherent platelets, preferentially mobilizes and recruits c-kit(-)/platelet-derived growth factor receptor (PDGFR)-beta(+)/lineage(-)/sca-1(+) progenitors for neointimal SMCs without being required for their differentiation. Hence, the SDF-1 alpha/CXCR4 axis is pivotal for vascular remodeling by recruiting a subset of SMC progenitors in response to apoptosis and in concert with platelets, epitomizing its importance for tissue repair and identifying a prime target to limit lesion development.