Urbich Carmen, Dimmeler Stefanie
Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Frankfurt, Germany.
Kidney Int. 2005 May;67(5):1672-6. doi: 10.1111/j.1523-1755.2005.00261.x.
Recent studies suggest that postnatal neovascularization relies not exclusively on sprouting of preexisting vessels ("angiogenesis"), but also involves the contribution of bone marrow-derived circulating endothelial progenitor cells (EPCs). EPCs can be isolated from peripheral blood or bone marrow mononuclear cells, CD34(+) or CD133(+) hematopoietic progenitors. Infusion of EPCs was shown to promote postnatal neovascularization of ischemic tissue after myocardial infarction in animal models and initial clinical trials. Moreover, circulating endothelial precursor cells can home to denuded arteries after balloon injury and contribute to endothelial regeneration, thereby limiting the development of restenosis. Thus, circulating endothelial cells may exert an important function as endogenous repair mechanism to maintain the integrity of the endothelial monolayer and to promote ischemia-induced neovascularization. However, risk factors for coronary artery disease, such as diabetes, hypercholesterolemia, and hypertension are associated with impaired number and function of EPC in patients with coronary artery disease. Therapeutically, the reduction of EPC number and the decreased functional activity in patients with coronary artery disease was counteracted by 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (statins), vascular endothelial growth factor (VEGF), estrogen, or exercise. At the molecular level, these factors are well established to activate the phosphatidyl-inositol-3-kinase (PI3K)-Akt-dependent activation of the endothelial nitric oxide synthase (eNOS), suggesting that the PI3K-Akt-eNOS signaling pathway may be involved in the transduction of atheroprotective factors. Taken together, the balance of atheroprotective and proatherosclerotic factors may influence EPC levels and their functional capacity to improve neovascularization and endothelial regeneration.
近期研究表明，出生后新血管形成不仅依赖于已有血管的芽生（“血管生成”），还涉及骨髓来源的循环内皮祖细胞（EPCs）的作用。EPCs可从外周血或骨髓单个核细胞、CD34(+)或CD133(+)造血祖细胞中分离出来。在动物模型和初步临床试验中，已表明输注EPCs可促进心肌梗死后缺血组织的出生后新血管形成。此外，循环内皮前体细胞可归巢至球囊损伤后的裸露动脉，并有助于内皮再生，从而限制再狭窄的发展。因此，循环内皮细胞可能作为一种内源性修复机制发挥重要作用，以维持内皮单层的完整性并促进缺血诱导的新血管形成。然而，冠状动脉疾病的危险因素，如糖尿病、高胆固醇血症和高血压，与冠状动脉疾病患者EPC数量和功能受损有关。在治疗方面，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂（他汀类药物）、血管内皮生长因子（VEGF）、雌激素或运动可抵消冠状动脉疾病患者EPC数量减少和功能活性降低的情况。在分子水平上，这些因素已被充分证实可激活磷脂酰肌醇-3-激酶（PI3K）-Akt依赖性的内皮型一氧化氮合酶（eNOS）激活，这表明PI3K-Akt-eNOS信号通路可能参与抗动脉粥样硬化因子的转导。综上所述，抗动脉粥样硬化和促动脉粥样硬化因子的平衡可能会影响EPC水平及其改善新血管形成和内皮再生的功能能力。
