Chronic High Glucose Concentration Induces Inflammatory and Remodeling Changes in Valvular Endothelial Cells and Valvular Interstitial Cells in a Gelatin Methacrylate 3D Model of the Human Aortic Valve.
Chronic High Glucose Concentration Induces Inflammatory and Remodeling Changes in Valvular Endothelial Cells and Valvular Interstitial Cells in a Gelatin Methacrylate 3D Model of the Human Aortic Valve.
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DOI：
10.3390/polym12122786
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发表时间：
2020-11-25
期刊：
影响因子：
5
通讯作者：
Manduteanu I
中科院分区：
文献类型：
--
作者：
Ciortan L;Macarie RD;Cecoltan S;Vadana M;Tucureanu MM;Mihaila AC;Droc I;Butoi E;Manduteanu I
钙化性主动脉瓣疾病（CAVD）是一种以炎症、纤维化和钙化为特征的退行性疾病，在糖尿病中加速。Hypertrophic通过仍然需要揭示的机制促进了这一过程。我们最近开发了一个基于明胶甲基丙烯酸酯的人主动脉瓣的3D模型，并揭示了高葡萄糖（HG）诱导成骨分子和增加钙沉积在促成骨环境中。为了进一步了解CAVD中糖尿病条件下导致钙化的事件，我们在这里分析了HG在我们的3D模型中诱导的炎症和重塑机制。将正常葡萄糖（NG）和高糖（HG）分别作用于瓣膜内皮细胞（VEC）和间质细胞（维克）7天和14天后，用抗CD 31免疫磁珠分离VEC和VIC。采用实时荧光定量PCR（RT-PCR）、Western blot、酶联免疫吸附试验（ELISA）和免疫荧光等方法，观察HG对大鼠海马神经元的影响。结果表明，HG诱导VEC和维克表达不同的细胞因子、细胞粘附分子和基质金属蛋白酶。此外，蛋白激酶C在VEC和维克中增加，表明与HG诱导的两种瓣膜细胞的炎症和重构相关的分子机制。这些发现可能为CAVD相关糖尿病的治疗提供新的生物标志物和靶点。
Calcific aortic valve disease (CAVD), a degenerative disease characterized by inflammation, fibrosis and calcification, is accelerated in diabetes. Hyperglycemia contributes to this process by mechanisms that still need to be uncovered. We have recently developed a 3D model of the human aortic valve based on gelatin methacrylate and revealed that high glucose (HG) induced osteogenic molecules and increased calcium deposits in a pro-osteogenic environment. To further understand the events leading to calcification in diabetic conditions in CAVD, we analyzed here the inflammatory and remodeling mechanisms induced by HG in our 3D model. We exposed valvular endothelial cells (VEC) and interstitial cells (VIC) to normal glucose (NG) or HG for 7 and 14 days, then we isolated and separated the cells by anti-CD31 immunomagnetic beads. The changes induced by HG in the 3D model were investigated by real-time polymerase chain reaction (RT-PCR), Western blot, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. Our results showed that HG induced expression of different cytokines, cell adhesion molecules and matrix metalloproteinases in VEC and VIC. In addition, protein kinase C was increased in VEC and VIC, indicating molecular mechanisms associated with HG induced inflammation and remodeling in both valvular cells. These findings may indicate new biomarkers and targets for therapy in diabetes associated with CAVD.
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DOI：
10.1073/pnas.90.20.9640
发表时间：
1993-10-15
影响因子：
11.1
作者：
ROTH, T;PODESTA, F;LORENZI, M
通讯作者：
LORENZI, M
人类急性心肌梗塞后心脏α（V）β（3）整联蛋白表达。
DOI：
10.1136/heartjnl-2016-310115
发表时间：
2017-04
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Jenkins WS;Vesey AT;Stirrat C;Connell M;Lucatelli C;Neale A;Moles C;Vickers A;Fletcher A;Pawade T;Wilson I;Rudd JH;van Beek EJ;Mirsadraee S;Dweck MR;Newby DE
通讯作者：
Newby DE
影响因子：
158.5
作者：
Cowell, SJ;Newby, DE;Boon, NA
通讯作者：
Boon, NA
影响因子：
3.5
作者：
Larsson, Susanna C.;Wallin, Alice;Wolk, Alicja
通讯作者：
Wolk, Alicja
影响因子：
158.5
作者：
Rossebo, Anne B.;Pedersen, Terje R.;Willenheimer, Ronnie
通讯作者：
Willenheimer, Ronnie