Prostaglandin F2α receptor silencing attenuates vascular remodeling in rats with type 2 diabetes

Exp Mol Pathol. 2015 Dec;99(3):517-23. doi: 10.1016/j.yexmp.2015.09.011. Epub 2015 Sep 25.

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.

Keywords: Diabetes; FP receptor; JNK; Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / physiology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Gene Silencing
  • Myocardium / metabolism
  • RNA, Small Interfering / genetics
  • Rats, Sprague-Dawley
  • Receptors, Prostaglandin / genetics
  • Receptors, Prostaglandin / metabolism*
  • Vascular Remodeling* / physiology

Substances

  • Blood Glucose
  • RNA, Small Interfering
  • Receptors, Prostaglandin
  • prostaglandin F2alpha receptor