Pathophysiological roles of heparin cofactor II in cardiac remodeling and insulin resistance

我们假设凝血酶失活可以改善心脏重塑和糖尿病。与野生型小鼠相比，内源性凝血酶抑制剂肝素辅助因子II（HCII）缺陷小鼠的血管紧张素II加速心脏同心重构，左心房容量增大，间质纤维化突出。这些心脏表型是由NAD(P) H氧化酶转化生长因子- β 1途径的增强引起的。此外，我们发现脂肪组织中凝血酶活性的增加通过增加MCP-1的产生，导致巨噬细胞浸润和胰岛素受体底物-1- akt通路失活，从而促进胰岛素抵抗的发展。

We hypothesized that thrombin inactivation ameliorate cardiac remodeling and diabetes. Angiotensin II accelerated cardiac concentric remodeling and larger left atrial volume with prominent interstitial fibrosis in heparin cofactor II(HCII), an endogenous thrombin inhibitor,-deficient mice than those in wild-type mice. And these cardiac phenotypes were caused by enhancement of NAD(P) H oxidase-transforming growth factor-beta1 pathway. In addition, we found that increased thrombin activity in adipose tissue contributes to the development of insulin resistance via enhancing MCP-1 production, leading to macrophage infiltration and insulin receptor substrate-1-Akt pathway inactivation.