Ya Li1, Lu Han1, Wen-Yuan Ding2, Yun Ti1, Yi-Hui Li1, Meng-Xiong Tang3, Zhi-Hao Wang4, Yun Zhang1, Wei Zhang1, Ming Zhong5. 1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Ji'nan, PR China; Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, PR China. 2. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Ji'nan, PR China; Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Ji'nan, PR China. 3. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Ji'nan, PR China; Department of Emergency, Qilu Hospital of Shandong University, Ji'nan 250012, PR China. 4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Ji'nan, PR China; Department of Geriatrics, Qilu Hospital of Shandong University, Ji'nan 250012, PR China. 5. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, the State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Ji'nan, PR China; Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan, PR China. Electronic address: zhongmingzm@gmail.com.
Abstract
BACKGROUND: Vascular remodeling is an important feature of diabetic macrovascular complications. The prostaglandin F2α receptor (FP), the expression of which is upregulated by insulin resistance and diabetes, is reportedly involved in myocardial remodeling. In this study, we aimed to investigate whether the FP receptor is implicated in diabetes-induced vascular remodeling. METHODS: A type 2 diabetic rat model was induced through a high-fat diet and low-dose streptozotocin (STZ). Thirty-two rats were randomized into four groups: control, diabetes, diabetes treated with empty virus and diabetes treated with FP receptor-shRNA. Then, we evaluated the metabolic index, FP receptor expression and vascular remodeling. We used FP receptor gene silencing in vivo to investigate the role that the FP receptor plays in the pathophysiologic features of vascular remodeling. RESULTS: Diabetic rats displayed increased levels of blood glucose, cholesterol, and triglycerides, as well as severe insulin resistance and FP receptor overexpression. In addition, increased medial thickness, excessive collagen deposition and diminished elastic fibers were observed in the diabetic rats, resulting in vascular remodeling. In the FP receptor-shRNA group, the medial thickness, collagen content, elastin/collagen ratio, and collagen I/collagen III content ratio were markedly decreased. Additionally, with FP receptor gene silencing, the JNK phosphorylation level was markedly decreased. CONCLUSIONS: Silencing of the FP receptor exerts a protective effect on diabetes-induced vascular remodeling, thereby suggesting a new therapeutic target for vascular remodeling in diabetes.
BACKGROUND: Vascular remodeling is an important feature of diabetic macrovascular complications. The prostaglandin F2α receptor (FP), the expression of which is upregulated by insulin resistance and diabetes, is reportedly involved in myocardial remodeling. In this study, we aimed to investigate whether the FP receptor is implicated in diabetes-induced vascular remodeling. METHODS: A type 2 diabeticrat model was induced through a high-fat diet and low-dose streptozotocin (STZ). Thirty-two rats were randomized into four groups: control, diabetes, diabetes treated with empty virus and diabetes treated with FP receptor-shRNA. Then, we evaluated the metabolic index, FP receptor expression and vascular remodeling. We used FP receptor gene silencing in vivo to investigate the role that the FP receptor plays in the pathophysiologic features of vascular remodeling. RESULTS:Diabeticrats displayed increased levels of blood glucose, cholesterol, and triglycerides, as well as severe insulin resistance and FP receptor overexpression. In addition, increased medial thickness, excessive collagen deposition and diminished elastic fibers were observed in the diabeticrats, resulting in vascular remodeling. In the FP receptor-shRNA group, the medial thickness, collagen content, elastin/collagen ratio, and collagen I/collagen III content ratio were markedly decreased. Additionally, with FP receptor gene silencing, the JNK phosphorylation level was markedly decreased. CONCLUSIONS: Silencing of the FP receptor exerts a protective effect on diabetes-induced vascular remodeling, thereby suggesting a new therapeutic target for vascular remodeling in diabetes.
Authors: Delnaz Roshandel; Ronald Klein; Barbara E K Klein; Bruce H R Wolffenbuttel; Melanie M van der Klauw; Jana V van Vliet-Ostaptchouk; Gil Atzmon; Danny Ben-Avraham; Jill P Crandall; Nir Barzilai; Shelley B Bull; Angelo J Canty; S Mohsen Hosseini; Linda T Hiraki; John Maynard; David R Sell; Vincent M Monnier; Patricia A Cleary; Barbara H Braffett; Andrew D Paterson Journal: Diabetes Date: 2016-04-12 Impact factor: 9.461