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Sequential study of gene expression profile in paraffin embedded endomyocardial biopsies: association with humoral rejection and cardiac allograft vasculopathy

Abstract

Heart transplantation poses significant opportunities for rehabilitation and survival for patients with heart failure refractory to clinical medical therapy. The main late complication and increasingly important as survival increases is cardiac allograft vasculopathy (VAC) with estimated incidence rate of 10% per year reaching 40-50% in recipients who have completed five years of postoperative period. The probably multifactorial pathogenesis is still controversial involving immunological (sex of the donor, HLA histocompatibility, rejection episodes) and non-immunological (hypertension, dyslipidemia, obesity, diabetes, ischemia time, recipient age, infection Cytomegalovirus) factors. The literature has increasingly shown that VAC process begins with endothelial injury and an imbalance of inflammatory factors and regulation can promote the pathogenesis of the disease.The aim of this study is to analyze sequential samples (first week, 3 and 6 months, 1 and 2 years of post-transplant) of paraffin-embedded endomyocardial biopsies from 60 transplant recipients. The immunohistochemical detection of complement fragment C4d will diagnose humoral rejection, and detection of C3b and C5b-9 complement will mark endothelial damage caused by the alternative pathway activation of the complement system. It will be also assessed by Real Time Polymerase Chain Reaction (RT-PCR) the expression of protective genes (HMOXO-1, NOS2, BCL2L1), adiponectin receptors (AdipoR1 and ADIPOR2) and genes associated to inflammatory injury ( IL-6, TNF, IFNg, TGF-², VEGF, and MCP-1).It is believed that by sequentially studying the endothelial injury mediated by the complement system activation and analyzing the gene expression involved in the humoral rejection process and VAC it would be possible to better understand the pathogenesis of the disease and proposing appropriate prevention to treat patients who underwent by heart transplantation. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LIN-WANG, HUI TZU; CIPULLO, REGINALDO; DIAS FRANCA, JOAO ITALO; FINGER, MARCO AURELIO; ROSSI NETO, JOAO MANOEL; CORREIA, EDILEIDE DE BARROS; DINKHUYSEN, JARBAS JACKSON; HIRATA, MARIO HIROYUKI. Intragraft vasculitis and gene expression analysis: Association with acute rejection and prediction of mortality in long-term heart transplantation. Clinical Transplantation, v. 32, n. 10, . (12/03605-8)

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