All-trans Retinoic Acid Attenuates Cardiac Allograft Vasculopathy in Rats

Objective. We sought to study the inhibitory effects of all-trans retinoic acid (ATRA) on cardiac allograft vasculopathy in rats. Methods. Inbred Wistar and Sprague-Dawley rats were used as donors and recipients, respectively. After abdominal heterotopic heart transplantation, animals were randomized to a cyclosporine (CsA) group versus a CsA+ATRA group: 10 mg/kg/d CsA versus the same CsA dose plus 10 mg/kg/d ATRA. Transplanted hearts were analyzed at 60 days. Cardiac allograft sections were treated with Van Giesson stain to examine vascular luminal occlusion, with immunohistochemistry for CD68 and proliferating cell nuclear antigen (PCNA), and with reverse-transcription polymerase chain reaction (RT-PCR) for platelet-derived growth factor A (PDGF-A) mRNA. Results. Luminal occlusion in the CsA+ATRA group was significantly less than that in the CsA group (40.10 +/- 8.20% vs 62.86 +/- 17.18%; P < .01). The CsA+ATRA group showed a marked reduction in PCNA- and CD68-positive cells: namely, 33.96 +/- 8.65% versus 60.17 +/- 17.74% (P < .01) and 17.63 +/- 4.24% versus 32.13 +/- 9.26 (P < .01), respectively. RT-PCR analysis showed that relative PDGF-A mRNA content in the CsA+ATRA group was significantly decreased compared with the CsA group (0.46 +/- 0.08 vs 0.94 +/- 0.11; P < .01). Conclusion. ATRA may attenuate rat cardiac allograft vasculopathy by inhibiting macrophage infiltration and cell proliferation.