Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model

Jun Neng Roan, Shih Yuan Fang, Shih Wei Chang, Chih Hsin Hsu, Chein Chi Huang, Meng Hsuan Chiou, Yu Chuan Tsai, Chen Fuh Lam

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Objective: This study investigates the pathogenesis of arteriovenous (AV) fistula failure in patients with diabetes mellitus (DM) and tests the vascular protective effect of rosuvastatin on the fistulous communication of diabetic rats. Methods: DM was induced in rats by a single injection of streptozotocin. One week later, a fistula was created in the descending aorta and the adjacent inferior vena cava (aortocaval [AC] fistula). Rats were then randomly assigned to receive placebo or rosuvastatin (15 mg/kg/d) in chow for 2 weeks. Blood flow in the aortic segments of the fistula was measured. Circulating CD34+/KDR+ endothelial progenitor cells (EPCs) were determined 2 weeks after creation of the AC fistulas using flow cytometry. Vascular function of the AC fistulas was assessed by isometric force testing. The expression of proinflammatory genes and generation of superoxide anions in the fistulas were examined. Results: The number of EPCs was reduced in diabetic rats, and rosuvastatin significantly increased the number of circulating EPCs. Reduced blood flow and impaired endothelium-dependent relaxation in the AC fistula of animals with diabetes was significantly potentiated after treatment with rosuvastatin. Rosuvastatin also attenuated the expression of inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate oxidase and generation of superoxide anions in the fistula tissues isolated from diabetic rats. Conclusions: We provide the first evidence demonstrating that rosuvastatin improves blood flow and endothelial function of AC fistulas in rats with DM by attenuating the activity of proinflammatory genes and generation of superoxide anions in the remodeled vasculature.

Original languageEnglish
Pages (from-to)1381-1389.e1
JournalJournal of Vascular Surgery
Volume56
Issue number5
DOIs
Publication statusPublished - 2012 Nov

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

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