Profiling of Circulating MicroRNAs After Heart Transplantation and During Acute Cellular and Antibody-Mediated Rejection

Introduction: Heart transplantation (HTx) is the definitive treatment for advanced heart failure. Despite universal immunosuppressive therapy, the threat of allograft rejection is persistent. Rejection is generally diagnosed by histology of graft myocardium obtained by biopsy which is invasive and prone to sampling error. Study of novel biomarkers such as circulating microRNAs (miRs) may allow noninvasive diagnosis of rejection. Methods: We studied serum levels of miRs associated with immune cell function (miR-155, 125b, 142-3p, 144, 223-3p, 27a and 101), myocardial damage (miR-1) and immunosuppression (let-7a). Blood was obtained from HTx recipients \u003e2 months post-HTx. Rejection was defined by histology of cardiac biopsy specimens and graded according to ISHLT guidelines. MiRs were analyzed with RT-PCR and normalized to 5S rRNA. Results: We analyzed samples from 12 healthy volunteers (44±6 yrs), 12 HTx recipients without evidence of rejection (54±11 yrs), 11 patients with acute cellular rejection (ACR; 4...