Decreased expression of ErbB2 on left ventricular epicardial cells in patients with diabetes mellitus.
Decreased expression of ErbB2 on left ventricular epicardial cells in patients with diabetes mellitus.
复制标题
糖尿病患者左心室心外膜细胞上ERBB2表达的降低。
DOI：
10.1016/j.cellsig.2022.110360
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发表时间：
2022-08
影响因子：
4.8
通讯作者：
Robich, Michael P.
中科院分区：
文献类型：
--
作者：
De Kay, Joanne T.;Carver, Joshua;Shevenell, Bailey;Kosta, Angela M.;Tsibulnikov, Sergey;Certo, Emily;Sawyer, Douglas B.;Ryzhov, Sergey;Robich, Michael P.
我们研究了冠状动脉旁路移植术（CABG）患者心脏活检获得的左心室（LV）心外膜内皮细胞和CD105+细胞表面ErbB受体的表达。内皮细胞和CD105+非内皮细胞从15例糖尿病患者和8例对照组的左室心外膜活检中新鲜分离。流式细胞术检测ErbB受体的表达。我们发现糖尿病（DM）和高水平的A1C血红蛋白与ErbB2表达降低相关。为了确定ErbB2受体的表达是否受葡萄糖水平的调节，我们研究了高葡萄糖对人微血管内皮细胞（HMEC-1）和CD105+非内皮细胞的影响，使用一种新的流式细胞术方法同时测定ErbB2的总水平、细胞表面表达和磷酸化。25 mM d -葡萄糖存在下的细胞孵育导致细胞表面下降，但没有ErbB2的总水平。细胞表面ErbB2水平受分解素和金属蛋白酶结构域蛋白10 （ADAM10）的调控，ADAM10在LV心外膜细胞上表达。抑制ADAM10可阻止ErbB2细胞表面表达的高葡萄糖依赖性下降。我们认为，高糖通过促进细胞表面ErbB2的adam10依赖性切割，抑制内皮细胞和心脏祖细胞中的ErbB受体信号，从而导致糖尿病患者的血管功能障碍和不良重塑。
We investigated the cell surface expression of ErbB receptors on left ventricular (LV) epicardial endothelial cells and CD105+ cells obtained from cardiac biopsies of patients undergoing coronary artery bypass grafting surgery (CABG). Endothelial cells and CD105+ non-endothelial cells were freshly isolated from LV epicardial biopsies obtained from 15 subjects with diabetes mellitus (DM) and 8 controls. The expression of ErbB receptors was examined using flow cytometry. We found that diabetes mellitus (DM) and high levels of hemoglobin A1C are associated with reduced expression of ErbB2. To determine if the expression of ErbB2 receptors is regulated by glucose levels, we examined the effect of high Glucose in human microvascular endothelial cells (HMEC-1) and CD105+ non-endothelial cells, using a novel flow cytometric approach to simultaneously determine the total level, cell surface expression, and phosphorylation of ErbB2. Incubation of cells in the presence of 25 mM D-glucose resulted in decreased cell surface but not total levels of ErbB2. The level of ErbB2 at the cell surface is controlled by disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) that is expressed on LV epicardial cells. Inhibition of ADAM10 prevented the high glucose-dependent decrease in the cell surface expression of ErbB2. We suggest that high Glucose depresses ErbB receptor signaling in endothelial cells and cardiac progenitor cells via the promotion of ADAM10-dependent cleavage of ErbB2 at the cell surface, thus contributing to vascular dysfunction and adverse remodeling seen in diabetic patients.
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影响因子：
37.8
作者：
Ho, FM;Liu, SH;Lin-Shiau, SY
通讯作者：
Lin-Shiau, SY
影响因子：
20.1
作者：
Hempel, A;Maasch, C;Haller, H
通讯作者：
Haller, H
DOI：
10.1073/pnas.1511175112
发表时间：
2015-11-24
影响因子：
11.1
作者：
Goth, Christoffer K.;Halim, Adnan;Schjoldager, Katrine T. -B. G.
通讯作者：
Schjoldager, Katrine T. -B. G.
影响因子：
6
作者：
Emani, Sirisha;Ramlawi, Basel;Sodha, Neel R.;Li, Jian;Bianchi, Cesario;Sellke, Frank W.
通讯作者：
Sellke, Frank W.
影响因子：
20.1
作者：
Feoktistov, I;Goldstein, AE;Biaggioni, I
通讯作者：
Biaggioni, I