Effect of sirolimus on the expression of integrin ανβ3 mRNA in cardiac allograft in rats

Abstract

Objective To investigate the effect of sirolimus (SRL) on the expression of integrin ανβ3 mRNA in vascular smooth muscle cells of cardiac allografts in rats, and the possible mechanism of SRL in the prevention of cardiac allograft vasculopathy. Methods Heterotopic heart transplantation models were established. Hearts from Wistar rats were heterotopically transplanted to SD rats (allograft) or Wistar rats (isograft). All rats were randomly divided into four groups:SRL group, SRL 1.25 mg/kg every day,oral intubation after cardiac transplantation; cyclosporine (CsA) group,CsA 10mg/kg every day, subcutaneous administration ; isograft group, no immunosuppressant administration;control group, normal hearts of Wistar rats. All of the animals were killed at 60 day after transplantation. Angiostenosis degree was analyzed by Mias system 4.1 after the cardiac tissues were stained with Van Gieson stain. Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect the expression of integrin ανβ3 mRNA in cardiac allografts. The relationship between the expression of integrin ανβ3 mRNA and the area of vascular stenosis was analyzed. ResultsIn control group, there was no thickened vascular intima and no vascular stenosis. In allograft group,the thickness of vascular intima was slightly increased but no vascular stenosis was detected. In CsA group, the vascular intima was obviously thickened, the lumen was narrowed, and some small arteries had obstruction. In SRL group, vascular intima proliferation and angiostenosis degree were obviously milder than in CsA group. Semiquantitative RT-PCR analysis revealed that the relative expression of integrin ανβ3 mRNA in CsA and SRL groups was increased significantly as compared with control group and isograft group (2.51±0.43 or 1.17±0.12 vs 0.28±0.08 or 0. 38 ± 0. 05, P＜0. 01). The relative expression of integrin ανβ3 mRNA in SRL group was decreased significantly as compared with CsA group (1.17±0.12 vs 2.51±0.43, P＜0.05). A positive correlation was found between vascular stenosis and the expression of integrin ανβ3 mRNA (r = 0. 654, P＜0. 01) in allografts. Conclusion SRL may down-regulate the expression of integrin ανβ3 mRNA in cardiac allografts in rats, which was probably associated with classic cardiac allograft vasculopathy. Key words: Sirolimus; Integrin alphavbeta3; Heart transplantation; Vasculopathy