Division of Cardiology, Department of Internal Medicine and Gene Therapy Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
Sci Rep. 2017 Mar 14;7:44473. doi: 10.1038/srep44473.
Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.
微血管功能障碍被认为在糖尿病心肌病中发挥重要作用。小富含亮氨酸的蛋白聚糖 decorin 通常被认为是一种促血管生成因子。在这里，我们研究了 decorin 的过表达是否可以改善糖尿病心肌病及其对体内和体外血管生成的影响。通过腹腔注射链脲佐菌素结合高脂肪饮食诱导糖尿病，并用重组腺相关病毒在 Wistar 大鼠中过表达 decorin。6 个月后，使用超声心动图和心导管系统测定心功能。结果表明，糖尿病大鼠的心脏功能下降，而过表达 decorin 则可以恢复。此外，过表达 decorin 上调了 VEGF 的表达，并减轻了心脏毛细血管密度的降低。在体外研究中，高葡萄糖诱导细胞凋亡并抑制管形成、迁移和增殖能力，而过表达 decorin 则可以改善这些能力。同时，decorin 过表达增加了 VEGF 和 IGF1R 的表达，以及 AKT 和 AP-1 的磷酸化水平。然而，IGF1R 抗体或 AKT 抑制剂预处理则可以消除所有这些作用。总之，过表达 decorin 通过 IGF1R-AKT-VEGF 信号通路改善了糖尿病心肌病，并促进了体内和体外的血管生成。
