Procalcific Phenotypic Drift of Circulating Progenitor Cells in Type 2 Diabetes with Coronary Artery Disease
Procalcific Phenotypic Drift of Circulating Progenitor Cells in Type 2 Diabetes with Coronary Artery Disease
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DOI：
10.1155/2012/921685
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Avogaro, Angelo
中科院分区：
文献类型：
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作者：
Fadini, Gian Paolo;Albiero, Mattia;Avogaro, Angelo
糖尿病（DM）改变与冠状动脉疾病（CAD）病理生理学相关的循环祖细胞。虽然内皮祖细胞（EPCs）减少，但没有关于循环祖细胞前钙化极化的数据，这可能有助于这些患者的血管钙化。在107例有或无DM和CAD的受试者队列中，我们分析了循环CD 34+祖细胞的促钙化与内皮分化状态。通过VEGFR-2（KDR）的表达和骨钙素（OC）和骨碱性磷酸酶（BAP）的表达来确定内皮定向和促钙化极化。我们发现，糖尿病患者有显着较高的表达OC和BAP循环CD 34+细胞比对照组，特别是在存在CAD。在糖尿病合并冠心病患者中，OC/KDR、BAP/KDR和OC+BAP/KDR的比值比其他组增加约3倍。从糖尿病患者CAD培养的EPCs偶尔形成高度提示钙化结节的结构，并且对照受试者的EPCs的成骨标志物的表达在对Toll样受体激动剂LPS的反应中显著增加。总之，糖尿病患者的循环祖细胞表现出向促钙化表型的表型漂移，其可能由炎症信号驱动。
Diabetes mellitus (DM) alters circulating progenitor cells relevant for the pathophysiology of coronary artery disease (CAD). While endothelial progenitor cells (EPCs) are reduced, there is no data on procalcific polarization of circulating progenitors, which may contribute to vascular calcification in these patients. In a cohort of 107 subjects with and without DM and CAD, we analyzed the pro-calcific versus endothelial differentiation status of circulating CD34+ progenitor cells. Endothelial commitment was determined by expression of VEGFR-2 (KDR) and pro-calcific polarization by expression of osteocalcin (OC) and bone alkaline phosphatase (BAP). We found that DM patients had significantly higher expression of OC and BAP on circulating CD34+ cells than control subjects, especially in the presence of CAD. In patients with DM and CAD, the ratio of OC/KDR, BAP/KDR, and OC+BAP/KDR was about 3-fold increased than in other groups. EPCs cultured from DM patients with CAD occasionally formed structures highly suggestive of calcified nodules, and the expression of osteogenic markers by EPCs from control subjects was significantly increased in response to the toll-like receptor agonist LPS. In conclusion, circulating progenitor cells of diabetic patients show a phenotypic drift toward a pro-calcific phenotype that may be driven by inflammatory signals.