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  1. Jing Zhang1,
  2. Jing Chen1,
  3. Jiawang Ding2,
  4. Changwu Xu1,
  5. Jian Yang2,
  6. Qing Guo3,
  7. Hong Jiang1,
  8. Hong Jiang1
  1. 1Department of Cardiology, Renmin Hospital of Wuhan University
  2. 2Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University
  3. 3Department of Ophthalmology, The First College of Clinical Medical Sciences, China Three Gorges University


    Objectives The neointimal hyperplasia is the common pathological basis of several vascular diseases, including atherosclerosis and restenosis. In recent years, a large number of studies have found that the oxidative stress after artery injury take a critical role in pathogenesis of intimal hyperplasia. Resveratrol as a polyphenols has showed significant antioxidant effect in a variety of diseases. However, it is unclear whether resveratrol participates in modulating vascular restenosis induced by oxidative injury after balloon injury.

    Methods The male Sprague-Dawley rats were established with balloon-injury model in vivo, and vascular smooth muscle cells (VSMCs) isolated from thoracic artery were stimulated with angiotensin II (Ang II) in vitro.

    Results Compared to model group, the neointimal/medial area (I/M) and the restenosis rate were both decreased significantly by 1mg/kg/d resveratrol intraperitoneal injection either 7 days or 14 days after surgery (I/M 7d:0.47±0.04 vs 0.13±0.02,p<0.05,14d:0.25±0.05 vs 1.06±0.08, p<0.05; Restenosis Rate 7d:0.08±0.03 vs 0.24±0.07,p<0.05,14d:0.09±0.03 vs 0.41±0.13, p<0.05).Moreover, the level of 8-iso-Prostaglandin F2a in serum were suppressed by 5.8 and 2.9 times after 7 days and 14 days respectively in resveratrol group compared to control group. The results of real-time PCR showed the MCP-1 and IL-6 mRNA expression in injured arteries were also inhibited by 4.27 and 3.06 times after 7 days and 14 days respectively with resveratrol. Interestingly, there was no significant difference of NF-κB p65 positive cell rate between resveratrol group and control group assayed by immunohistochemistry (7 d p=0.54; 14 d p=0.82).The CCK-8 test and transwell method suggested VSMCs pretreated with 200 µmol/l resveratrol represented a blunted response to proliferation and migration in the presence of 1 µmol/l Ang II(p<0.001, p<0.05).Moreover, the intracellular ROS levels was decreased significantly in resveratrol pretreatment group (p<0.001).Meanwhile, the NADPH oxidase activity was significantly suppressed (p<0.05) and SOD activity was notably enhanced (58.99±0.38 vs. 37.09±1.29,p<0.001). Western blot results revealed that resveratrol could suppress the ERK phosphorylation and NF-κB transcriptional activity (both p<0.001),with no effects on NF-κB p65 translocation and IkB degradation (both p>0.05).

    Conclusions Resveratrol could significantly suppressed neointimal hyperplasia after balloon injury though inhibition of oxidative stress and inflammation.

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