Fadini Gian Paolo, Albiero Mattia, Menegazzo Lisa, Boscaro Elisa, Agostini Carlo, de Kreutzenberg Saula Vigili, Rattazzi Marcello, Avogaro Angelo
Department of Clinical and Experimental Medicine, University of Padova, 35128 Padova, Italy.
Exp Diabetes Res. 2012;2012:921685. doi: 10.1155/2012/921685. Epub 2012 Feb 28.
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.
糖尿病（DM）会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）数量减少，但关于循环祖细胞的促钙化极化情况尚无数据，而这可能导致这些患者的血管钙化。在一个包含107名有或无DM及CAD的受试者队列中，我们分析了循环CD34 +祖细胞的促钙化与内皮分化状态。通过血管内皮生长因子受体2（VEGFR - 2，KDR）的表达来确定内皮细胞分化，通过骨钙素（OC）和骨碱性磷酸酶（BAP）的表达来确定促钙化极化。我们发现，DM患者循环CD34 +细胞上OC和BAP的表达显著高于对照组，尤其是在合并CAD的情况下。在患有DM和CAD的患者中，OC/KDR、BAP/KDR以及OC + BAP/KDR的比值比其他组增加了约3倍。从患有CAD的DM患者中培养的EPCs偶尔会形成高度提示钙化结节的结构，并且对照组受试者的EPCs对Toll样受体激动剂LPS的反应中，成骨标志物的表达显著增加。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，这可能由炎症信号驱动。
