HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation
Hitoshi HorimotoShinjiro Sasaki

Abstract

The development of atherosclerotic cardiovascular complications caused by hyperlipidemia is a common and serious problem for long-term survivors of organ transplantation. However, adhesion molecules such as intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 are involved in allograft rejection, possibly by providing costimulatory signals. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor cerivastatin has been shown to suppress ICAM-1 expression in acute inflammatory responses. In this study, we evaluated the immunosuppressive effects of cerivastatin in rat cardiac allografts. The hearts of Fischer rats were transplanted heterotopically into Lewis rats. Cerivastatin (2 mg/kg) was administrated intraperitoneally to recipients for 7 consecutive days from the day before transplantation. Graft survival in the cerivastatin-treated group (n = 8) was significantly longer than in controls (n = 10) (24.6 +/- 2.2 days vs 10.2 +/- 1.3 days, p < 0.05). Mixed lymphocyte reaction (MLR) showed that on Day 8 after grafting, the proliferative response of alloreactive T cells against F344 alloantigen in cerivastatin-treated rats was significantly more suppressed than in Lewis rats. The Int...Continue Reading

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Citations

Sep 7, 2005·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Todd J GraziaBiagio A Pietra
Jun 29, 2010·Langenbeck's Archives of Surgery·Mohammed Reza MoussavianMichael D Menger
Nov 26, 2010·Journal of Cardiovascular Pharmacology·Robert Krysiak, Boguslaw Okopien
Jan 1, 2003·World Journal of Gastroenterology : WJG·Yan-Ling YangKai-Zong Li
Jan 3, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Teodor-D BrumeanuSofia Casares

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