Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.
Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.
复制标题
核心蛋白聚糖过度表达通过 IGF1R-AKT-VEGF 信号促进糖尿病心肌病的血管生成
DOI：
10.1038/srep44473
复制
发表时间：
2017-03-14
影响因子：
4.6
通讯作者：
Wang DW
中科院分区：
文献类型：
--
作者：
Lai J;Chen F;Chen J;Ruan G;He M;Chen C;Tang J;Wang DW
微循环障碍被认为在糖尿病心肌病中起重要作用。富含亮氨酸的小蛋白聚糖核心蛋白聚糖通常被认为是促血管生成因子。在这里，我们研究核心蛋白聚糖的过度表达是否能改善糖尿病性心肌病及其在体内和体外对血管生成的影响。通过腹腔注射链脲佐菌素结合高脂饮食诱导糖尿病，并通过重组腺相关病毒在Wistar大鼠中过表达核心蛋白聚糖。六个月后，使用超声心动图和心导管系统确定心脏功能。结果表明，糖尿病大鼠心功能下降，核心蛋白聚糖过表达可使其恢复。此外，核心蛋白聚糖的过表达上调VEGF的表达，并减弱心脏毛细血管密度的降低。在体外研究中，高糖诱导细胞凋亡，抑制小管形成、迁移和增殖的能力，而核心蛋白聚糖过表达可改善这些能力。同时，decorin过表达增加VEGF和IGF 1 R的表达，以及AKT和AP-1的磷酸化水平。尽管如此，所有这些作用都被IGF 1 R抗体或AKT抑制剂预处理所消除。总之，在体内和体外，核心蛋白聚糖的过度表达通过IGF 1 R-AKT-VEGF信号通路改善糖尿病心肌病并促进血管生成。
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.