Silencing of activin receptor-like kinase 7 alleviates aortic stiffness in type 2 diabetic rats

Aim: Arterial stiffness is an important feature of diabetic macrovascular complications. Activin receptor-like kinase 7 (ALK7), a member of type I Transforming Growth Factor-β (TGF-β) receptors, is correlated with pathogenic risks of type 2 diabetes mellitus and cardiovascular diseases and may be involved in cardiovascular remodeling. We aimed to investigate whether ALK7 is implicated in diabetes-induced aortic stiffness.

Methods: Type 2 diabetes was induced by high-fat diet and low-dose streptozotocin (STZ; 27.5 mg/kg). Forty rats were separated into four groups: control, diabetes, diabetes with empty virus and diabetes treated with ALK7-shRNA. The metabolic index, ALK 7 expression and aortic stiffness were evaluated. We used gene silencing method to investigate the role of ALK7 in the pathological development.

Results: Diabetic rats showed increased blood glucose, Cholesterol, triglyceride levels, severe Insulin resistance and ALK7 overexpression. Diabetes enhanced aortic stiffness, as demonstrated by the loss and disruption of elastic fibers as well as by an increase in collagen fibers in the aortic media. ALK7 gene silencing ameliorated metabolic hyperlipidemia and Insulin resistance. With ALK7 gene silencing, collagen content, elastin to collagen ratio, as well as collagen I-to-collagen III content ratio in diabetic rats were significantly decreased. Moreover, the phosphorylation level of SMAD2/3 was markedly decreased after ALK7 gene silencing.

Conclusions: ALK7 gene silencing has a protective effect on diabetes-induced aortic stiffness, Insulin resistance and hyperlipidemia, thus implicating a new potential therapeutic approach to diabetic macrovascular stiffness.