Tranilast inhibits transplant-associated coronary arteriosclerosis in a murine model of cardiac transplantation.
Accelerated coronary arteriosclerosis remains a major problem for the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood and there is no effective therapy. Tranilast is a promising drug that may prevent post-angioplasty restenosis. Here, we investigated whether orally administered tranilast inhibits the development of intima hyperplasia in a mouse model of cardiac transplantation. Cardiac allografts from BALB/c mice were transplanted heterotopically into C3H/He mice. Mice were administered either vehicle or tranilast everyday by gavage. Morphometrical analysis of the cardiac allografts harvested at 2 months revealed that the administration of tranilast significantly reduced the development of coronary atherosclerosis. In the mice treated with tranilast, up-regulation of the cyclin-dependent kinase inhibitor p21 was observed in the allografts, accompanied by a reduced number of proliferating cells. Tranilast also suppressed transforming growth factor-beta (TGF-beta) expression. Tranilast may be effective in preventing transplant-associated arteriosclerosis through its anti-inflammatory and anti-proliferative effects.
Saiura
A
A
Department of Surgery, University of Tokyo, Graduate School of Medicine, Tokyo 113-8655, Japan.
Sata
M
M
Hirata
Y
Y
Nagai
R
R
Makuuchi
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D003324:Coronary Artery Disease / Q000517:prevention & control*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D016027:Heart Transplantation / Q000009:adverse effects*; D006965:Hyperplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; C012293:tranilast