Functional and molecular determinants of right ventricular response to severe pulmonary hypertension in a large animal model
R. Dale Brown, Kendall S. Hunter, Min Li, Maria G. Frid, Julie W. Harral, Greta M. Krafsur, Timothy N. Holt, Jason S. Williams, Hui Zhang, Suzette Riddle, Michael G. Edwards, Sushil Kumar, Cheng‐Jun Hu, Brian B. Graham, Lori A. Walker, Franklyn B. Garry, Peter M. Buttrick, Tim Lahm, Vitaly O. Kheyfets, Kirk C. Hansen, Kurt R. Stenmark
Abstract
Using a large animal model and employing a comprehensive approach integrating hemodynamic, transcriptomic, proteomic, and immunohistochemical analyses, we examined the early (2 wk) effects of severe PH on the RV. We observed that RV remodeling during PH progression represents a continuum of transcriptionally driven processes whereby cardiac myocytes, fibroblasts, endothelial cells, and proremodeling macrophages act to coordinately maintain physiological homeostasis and protect myocyte survival during chronic, severe, and progressive pressure overload.