HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway
HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway
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DOI：
10.1172/jci13152
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发表时间：
2001-08-01
影响因子：
15.9
通讯作者：
Zeiher, AM
中科院分区：
文献类型：
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作者：
Dimmeler, S;Aicher, A;Zeiher, AM
HMG-CoA还原酶抑制剂(他汀类)已被开发为降脂药物，已被广泛用于降低冠心病的发病率和死亡率。在这里，我们证明了他汀类药物能有效地促进从外周血分离的单个核细胞和CD34阳性造血干细胞中内皮祖细胞的分化。此外，他汀类药物治疗增加了小鼠骨髓中c-kit(+)/SCA-1(+)阳性的造血干细胞，并进一步增加了分化的内皮祖细胞(EPC)的数量。他汀类药物通过PI3K/Akt(PI3K/Akt)途径诱导EPC分化，药理PI3K阻滞剂的抑制作用或显性负Akt结构的过度表达证明了这一点。同样，强大的血管生成生长因子血管内皮生长因子需要Akt来增加EPC数量，这表明Akt在调节造血祖细胞分化方面发挥了重要作用。鉴于他汀类药物在促进内皮祖细胞分化方面至少与血管内皮细胞生长因子一样有效，循环内皮祖细胞的增加可能对他汀类药物在冠心病患者中的良好效果做出重要贡献。
HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)-positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.