Cardiac allograft vasculopathy (CAV) is a major limiting factor in the long-term success of heart transplantation. Ischemia-reperfusion injury plays a critical role in initiation of cardiac graft rejection and graft vasculopathy. miR-499 is a cardiac-abundant miRNA under physiological conditions and it has been recently demonstrated that over-expression of miR-499 can prevent cardiomyocyte apoptosis induced by ischemia-reperfusion injury and regulate cardiac remodeling. In this study, we investigated the role of over-expression of miR-499 within donor heart in the pathogenesis of CAV.
Donor hearts were obtained from wild-type B6 (WT) and miR-499 transgenic B6 mice, which highly express miR-499 in the heart, and were transplanted into MHC classII-mismatched bm12 recipients. The transplanted hearts were harvested at 24 hours and 8 weeks after transplantation for evaluation of ischemia-reperfusion injury and CAV. Ischemia-reperfusion injury was determined by histology and the release of CK and LDH. The severity of vasculopathy was determined by the percentage of arterial occlusion and myocardial fibrosis.
All heart grafts in both groups had palpable contraction at 8 weeks after transplantation. However, heart grafts in WT group developed severe arterial occlusion (77.7±2.4%), while miR-499 transgenic heart grafts had markedly less arterial occlusion (42.0±3.0%, P<0.001) and less myocardiac fibrosis.
Donor hearts from miR-499 transgenic mice significantly reduced the release of CK and LDH as compared to WT donors (3667±194.7 vs. 5043±523.8U/L, P=0.03 and 684±19.1 vs. 1068±150.0U/L, P=0.03, respectively) and exhibited lower degree of perivascular inflammation, leukocyte infiltration and myocyte necrosis 24 hours after transplantation.
These data indicates that over-expression of miR-499 can reduce ischemia/reperfusion-elicited myocardial tissue injury and attenuate CAV in the long-term. Our study suggests that modulation of miR-499 in donor heart may be a promising therapeutic approach for preventing CAV.
To cite this abstract in AMA style:Zhang X, Chen Z, Chen X, Li P, Yang J. Over-Expression of miR-499 within Donor Heart Attenuates Cardiac Allograft Vasculopathy [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/over-expression-of-mir-499-within-donor-heart-attenuates-cardiac-allograft-vasculopathy/. Accessed January 21, 2021.
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