(875) - Localization of microRNAs in Cardiac Allograft Vasculopathy With In Situ Hybridization; a Role in Immune Regulation and/or Fibrosis?

Abstract

s S315 Methods: Q-PCR analysis of CAV intima samples showed 5 miRs to have a significant up(miR-21, -223, and -146b-5p) or down-regulation (miR886-5p and -214) compared to control intima. The four main cell types within the intima (mononuclear cells, endothelial cells, vascular smooth muscle cells, and fibroblasts) were analyzed in vitro for their miR expression by Q-PCR. Using LNA-probes for In Situ Hybridization of these specific miRs the localization within each cell and between different cells types was determined in CAV tissue sections. Eight HTx-patients, with or without CAV, were included in this analysis. Results: Literature and in vitro experiments suggested two main cell categories that could express these miRs: miR-146b and -223 are mainly detected in immune cells and miR-21, -214, and -886-5p mainly in fibroblasts, smooth muscle, and/or endothelial cells. Most miRs show no or little expression in healthy coronary arteries. In CAV arteries miR-214 and -886-5p are highly expressed in macrophages. In more fibrotic CAV lesions less mR-214 and -886-5p was observed and the expression of miR-223 is highly increased in the extra cellular matrix. MiR-21 and -223 remain low, but when present located in elongated, probably fibroblast like, cells and lymphocytes, respectively. Conclusion: The type of cells positive for one miR did not change as CAV progresses, but because the cellular profile changes in the arterial wall, miR expression patterns change. This study confirms that these miRs play a role in the immunological or fibrotic process of CAV. Interfering with this miR expression could be an interesting new therapeutic approach. is too recent to document visitation. Altogether, the tutorial is available to over 1.2 billion people in their native language. The utility of the tutorial is being assessed through an on-line evaluation. Conclusion: The AECVP and SCVP have together generated the first complete web-tutorial for the interpretation of ACR on EMB available at www. scvp.net. With its translation into multiple languages, the tutorial has become the most universal treatise on acute cellular rejection. This should improve inter-institution agreement on cellular rejection.