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Anti-inflammatory effects of simvastatin during the resolution phase of experimentally formed venous thrombi
  1. Yaping Feng1,
  2. Bo Lei2,
  3. Fuxian Zhang1,
  4. Luyuan Niu1,
  5. Huan Zhang1,
  6. Mingyi Zhang1
  1. 1Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
  2. 2Anesthesia Department, Beijing Haidian Maternal & Child Health Hospital, Beijing, China
  1. Correspondence to Dr Fuxian Zhang, Department of Vascular Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; leibo1977{at}163.com

Abstract

Deep venous thrombosis (DVT) is a common vascular disease and is closely linked to inflammation. Over the past decade, the potential antithrombotic effect of statins has been elucidated by clinical studies, primarily through focusing on DVT prevention. The effects of statins on DVT resolution and its underlying mechanisms have been rarely addressed. We established a rabbit model of the inferior vena cava (IVC) venous thrombosis. After 48 hours, the rabbits were treated with saline, heparin, simvastatin, or simvastatin combined with heparin, respectively, for 14 days. The migration of inflammatory cells (neutrophils, monocytes, lymphocytes) in the thrombi and injured venous wall, the plasma levels of interleukin (IL)-6, monocyte chemotactic protein 1 (MCP-1) and P-selectin, and local expression of MCP-1 and P-selectin in the venous wall were evaluated by histology, immunohistochemistry, and ELISA examinations. Our data showed that compared with saline and heparin controls, monotherapy of simvastatin and the adjunctive therapy with simvastatin and heparin significantly improved the thrombus resolution and reduced inflammatory cells migration into the venous wall, the release of the inflammatory cell adhesion molecule (P-selectin), inflammatory chemokine (MCP-1) and pleiotropic proinflammatory cytokines (IL-6) into the blood, and the local expression of P-selectin and MCP-1 in the venous wall. Simvastatin targets anti-inflammatory pathways during the resolution phase of a thrombus, providing a therapeutic potential in DVT resolution and post-thrombotic syndrome prevention.

  • Vascular Diseases

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Footnotes

  • Contributors The authors declare that all the listed authors have participated actively in the study and all meet the requirements of authorship. YF and FZ designed the study and wrote the protocol, YF, BL and LN performed the research/study; YF and HZ managed the literature searches and analyses; YF and MZ undertook the statistical analysis; and YF wrote the first draft of the manuscript.

  • Competing interests None declared.

  • Ethics approval The animal studies were performed in accordance with the institution guidelines for laboratory animal research; it has been approved by the Ethics Committee of Beijing Shijitan Hospital, Capital Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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