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Enhancing the Expression of CFTR Using Antisense Molecules against MicroRNA miR-145-5p

2019; American Thoracic Society; Volume: 199; Issue: 11 Linguagem: Inglês

10.1164/rccm.201901-0019le

1535-4970

Alessia Finotti, Jessica Gasparello, Enrica Fabbri, Anna Tamanini, Roberto Corradini, Maria Cristina Dechecchi, Giulio Cabrini, Roberto Gambari,

MicroRNA in disease regulation

group (P = 0.0053), suggesting a directly nephroprotective role of NO.However, no assesment of right heart function and no detailed hemodynamic measurements were presented.To determine both the cardiac and renal protective effects of NO during cardiac surgery and the potential cardio-renal interactions that might occur, we are now conducting a randomized trial in 250 cardiac surgery patients at the Massachusetts General Hospital (Boston, MA) with intraoperative echocardiography and pulmonary artery catheterization.We will measure renal biomarkers, assess pre-and postoperative redox states, and evaluate pre-and postoperative levels of plasma NO metabolomics.The primary endpoint of this ongoing study in Boston is to determine whether NO is effective in the prevention of AKI as defined by Kidney Disease Improving Global Outcomes criteria (ClinicalTrials.govIdentifier: NCT02836899).However, in contrast to our first trial in China in patients primarily with rheumatic heart disease, Americans undergoing heart surgery are generally older and are affected by endothelial dysfunction.Endothelial dysfunction is a condition characterized by impaired endothelial NO synthase.In these patients, the diseased endothelium is unable to provide appropriate vasodilation during and after ischemic events, and is unable to replenish plasma NO after consumption of NO from intravascular hemolysis (5).At present (January 2019), we are halfway through enrollment (n = 125).We believe that the results of this ongoing trial will be able to address the hypothesis of Dr. Coutrot and colleagues.