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Cytochrome p450 2C Contributes to Peri‐Transplant Ischemic Injury and Cardiac Allograft Vasculopathy Following Heterotopic Heart Transplantation in Rats
Author(s) -
Hunter Arwen L,
Kerjner Alexandra,
Mueller Katelyn J,
McManus Bruce M,
Granville David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1123.29
Subject(s) - tunel assay , medicine , infiltration (hvac) , transplantation , immune system , apoptosis , myocardial infarction , cardiology , cytochrome c , reperfusion injury , ischemia , immunohistochemistry , pathology , urology , immunology , biology , biochemistry , physics , thermodynamics
Peritransplant ischemia and reperfusion (I/R) injury contributes to post‐transplant vascular dysfunction and cardiac allograft vasculopathy (CAV). We have shown that cytochrome p450 (CYP) 2C inhibition significantly reduces I/R‐induced myocardial infarction and post‐ischemic vascular dysfunction. The objective of this study was to assess the contribution of CYP2C to CAV. Rat heterotopic heart transplants were performed between Lewis donors and Fisher recipients. Rats received CYP2C inhibition by sulfaphenazole (SP) or vehicle control 1hr prior to surgery. Organs were harvested 4, 7 and 30 days post‐transplant. Luminal narrowing was measured using morphometric analysis and immune infiltration was scored from absent to severe in a blinded manner. Smooth muscle cell (SMC) proliferation and apoptotic cells were detected by Ki‐67 and TUNEL staining, respectively. SP did not affect post‐transplant morbidity, mortality or weight gain. Coronary blood vessels from rats treated with SP showed significantly reduced luminal narrowing compared to control (12.07±4.09% vs 66.21±13.61%, p<0.05) and demonstrated a reduced SMC proliferation (3.32±3.27% vs. 7.20±2.32%). SP did not alter immune infiltration (p>0.1) nor did it significantly alter TUNEL positivity in myocardial, endothelial or SMC populations. In conclusion, CYP2C contributes to SMC proliferation CAV without affecting general immune infiltration.