HMG-CoA reductase inhibitor cerivastatin prolonged rat cardiac allograft survival by blocking intercellular signals
| Autor: | Shinjiro Sasaki, Yasunari Nakai, Yukiya Nomura, Ken ich Nakahara, Shigetoshi Mieno, Hitoshi Horimoto |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Pyridines medicine.medical_treatment Intercellular Adhesion Molecule-1 Organ transplantation Internal medicine Immune Tolerance Leukocytes Animals Medicine Heart transplantation Transplantation biology business.industry Graft Survival Models Cardiovascular Cerivastatin Intercellular adhesion molecule Immunohistochemistry Hydroxymethylglutaryl-CoA reductase Lymphocyte Function-Associated Antigen-1 Rats Inbred F344 Rats Disease Models Animal Treatment Outcome Endocrinology Rats Inbred Lew HMG-CoA reductase biology.protein Heart Transplantation Interleukin-2 Surgery Hydroxymethylglutaryl-CoA Reductase Inhibitors Lymphocyte Culture Test Mixed Cardiology and Cardiovascular Medicine business Signal Transduction medicine.drug |
| Zdroj: | The Journal of Heart and Lung Transplantation. 21:440-445 |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/s1053-2498(01)00403-x |
| Popis: | 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, p0.05). 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 Interleukin-2 concentration of supernatant in MLR cultures in the cerivastatin-treated group was lower than in the control group. Immunohistochemical analysis showed that the percentage of CD4-positive cells to infiltrating mononuclear cells was less prominent in the cerivastatin-treated group (9.8% +/- 2.2%) than in the control group (20.9% +/- 3.2%).The HMG-CoA reductase inhibitor cerivastatin effectively suppressed acute graft rejection, possibly by blocking intercellular signals via ICAM/LFA-1, and cerivastatin may be a candidate for treating patients with hyperlipidemia who undergo organ transplantation. |
| Databáze: | OpenAIRE |
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