John Park, MD, PhD, Justine Liang, MD, MS, and Soban Umar, MD, PhD: Electrical Remodeling in Right Ventricular Failure Due to Pulmonary Hypertension: Unraveling Novel Therapeutic Targets
Published on February 27, 2023
CA-2 Resident Physicians John Park, MD, PhD, and Justine Liang, MD, MS, published a paper in the International Journal of Molecular Sciences with Soban Umar, MD, PhD, Associate Professor and Associate Program Director for Resident Research, who served as senior author on the paper. Dr. Park is part of the Anesthesiology Resident Research Pathway (ARRP) under the mentorship of Dr. Umar and has earned multiple accolades throughout his training, including the 2nd Place Award for ASA Residents' Research Essay Contest at the ASA Annual Meeting in 2022 and the 1st Place Oral Presentation Award at the WARC Annual Meeting in 2022. In this project, Drs. Park, Liang, and Umar explore the underlying mechanism of electrical remodeling in right ventricular failure due to pulmonary hypertension.
Abstract
"Arrhythmias in the setting of right-ventricular (RV) remodeling contribute to majority of deaths in patients with pulmonary hypertension. However, the underlying mechanism of electrical remodeling remains elusive, especially ventricular arrhythmias. Here, we analyzed the RV transcriptome of pulmonary arterial hypertension (PAH) patients with compensated RV or decompensated RV and identified 8 and 45 differentially expressed genes known to be involved in regulating the electrophysiological properties of excitation and contraction of cardiac myocytes, respectively. Transcripts encoding voltage-gated Ca2+ and Na+ channels were notably decreased in PAH patients with decompensated RV, along with significant dysregulation of KV and Kir channels. We further showed similarity of the RV channelome signature with two well-known animal models of PAH, monocrotaline (MCT)- and Sugen-hypoxia (SuHx)-treated rats. We identified 15 common transcripts among MCT, SuHx, and PAH patients with decompensated RV failure. In addition, data-driven drug repurposing using the channelome signature of PAH patients with decompensated RV failure predicted drug candidates that may reverse the altered gene expression. Comparative analysis provided further insight into clinical relevance and potential preclinical therapeutic studies targeting mechanisms involved in arrhythmogenesis."
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