Cell death‐inducing DFF45‐like effector C gene silencing alleviates pulmonary vascular remodeling in a type 2 diabetic rat model

AIMS/INTRODUCTION: Cell death‐inducing DFF45‐like effector C (CIDEC) was proven to be closely associated with the development of insulin resistance and metabolic syndrome. We aimed to investigate whether CIDEC gene silencing could alleviate pulmonary vascular remodeling in a type 2 diabetes rat model. MATERIALS AND METHODS: We built a type 2 diabetes rat model. An adenovirus harboring CIDEC small interfering ribonucleic acid was then injected into the jugular vein to silence the CIDEC gene. After hematoxylin–eosin and Sirius red staining, we detected indexes of the pulmonary arterioles remodeling. Immunohistochemical staining of proliferating cell nuclear antigen was used to evaluate the pulmonary arterial smooth muscle cell proliferation. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling reaction and western blotting. The levels of signaling pathway proteins expression were measured by western blotting analyses. RESULTS: Histological analysis of the pulmonary artery showed that the thickness of the adventitia and medial layer increased notably in type 2 diabetes rats. Immunohistochemistry showed that more proliferating cell nuclear antigen‐positive pulmonary arterial smooth muscle cells could be seen in type 2 diabetes rats; and after CIDEC gene silencing, proliferating cell nuclear antigen positive cells decreased accordingly. Cleaved caspase‐3 and cleaved poly (adenosine diphosphate‐ribose) polymerase measured by western blotting showed increased apoptosis with overexpressed CIDEC in diabetes. Terminal deoxynucleotidyl transferase dUTP nick end labeling reaction showed that the apoptosis mainly occurred in endothelial cells. Western blotting analysis showed CIDEC overexpression in rats with diabetes, and phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α expression was significantly decreased. After CIDEC gene silencing, the expression of phosphorylated adenosine 5′ monophosphate‐activated protein kinase‐α was upregulated. CONCLUSIONS: The CIDEC/5′ monophosphate‐activated protein kinase signaling pathway could be a potential therapeutic candidate against pulmonary vascular diseases in type 2 diabetes patients.