Myocardial cell death in human diabetes
Myocardial cell death in human diabetes
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DOI：
10.1161/01.res.87.12.1123
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发表时间：
2000-12-08
影响因子：
20.1
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Frustaci, A;Kajstura, J;Anversa, P
肾素-血管紧张素系统与糖尿病上调，这可能有助于发展扩张性肌病。血管紧张素Il （Ang II）可局部导致氧化损伤，激活心肌细胞死亡。此外，糖尿病和高血压可协同损害心肌结构和功能。因此，我们在糖尿病和糖尿病高血压患者的心室心肌活检中测量了细胞凋亡和坏死。氧化应激标志物、硝基酪氨酸和Ang II标记的积累进行了定量评估。糖尿病热表现为心脏肥厚、腔体扩张和心室功能下降。这些改变在糖尿病和高血压患者中更为严重。糖尿病的特点是肌细胞、内皮细胞和成纤维细胞的凋亡分别增加85倍、61倍和26倍。糖尿病和高血压患者心肌细胞凋亡没有增加。糖尿病使肌细胞坏死增加4倍，内皮细胞坏死增加18倍，成纤维细胞坏死增加6倍。然而，糖尿病和高血压使肌细胞坏死增加7倍，内皮细胞坏死增加18倍。同样，与糖尿病合并高血压患者相比，糖尿病合并高血压患者肌细胞和内皮细胞中的Ang II标记增加更多。硝基酪氨酸在心脏细胞中的定位也遵循类似的模式。尽管糖尿病患者与糖尿病合并高血压患者的硝基酪氨酸阳性细胞数量不同，但仅在含有这种修饰氨基酸的细胞中检测到肌细胞、内皮细胞和成纤维细胞的凋亡和坏死。综上所述，糖尿病和糖尿病合并高血压患者体内Ang II的局部升高可增强氧化损伤，激活心肌细胞凋亡和坏死。
The renin-angiotensin system is upregulated with diabetes, and this may contribute to the development of a dilated myopathy. Angiotensin Il (Ang II) locally may lead to oxidative damage, activating cardiac cell death. Moreover, diabetes and hypertension could synergistically impair myocardial structure and function. Therefore, apoptosis and necrosis were measured in ventricular myocardial biopsies obtained from diabetic and diabetic-hypertensive patients. Accumulation of a marker of oxidative stress, nitrotyrosine, and Ang II labeling were evaluated quantitatively. The diabetic heat showed cardiac hypertrophy, cavitary dilation, and depressed ventricular performance. These alterations were more severe with diabetes and hypertension. Diabetes was characterized by an 85-fold, 61-fold, and 26-fold increase in apoptosis of myocytes, endothelial cells, and fibroblasts, respectively. Apoptosis in cardiac cells did not increase additionally with diabetes and hypertension. Diabetes increased necrosis by 4-fold in myocytes, 18-fold in endothelial cells, and 6-fold in fibroblasts. However, diabetes and hypertension increased necrosis by 7-fold in myocytes and 18-fold in endothelial cells. Similarly, Ang II labeling in myocytes and endothelial cells increased more with diabetes and hypertension than with diabetes alone. Nitrotyrosine localization in cardiac cells followed a comparable pattern. In spite of the difference in the number of nitrotyrosine-positive cells with diabetes and with diabetes and hypertension, apoptosis and necrosis of myocytes, endothelial cells, and fibroblasts were detected only in cells containing this modified amino acid. In conclusion, local increases in Ang II with diabetes and with diabetes and hypertension may enhance oxidative damage, activating cardiac cell apoptosis and necrosis.