Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

MULTISCALE MODELING FOR DETERMINING SEX DIFFERENCES IN RESTING AND ACTIVE MYOCARDIAL MATERIAL PROPERTIES IN A RAT PAH MODEL Daniela Valdez-Jasso 1 ; 1 University of California San Diego, Bioengineering, La Jolla, CA, USA Pulmonary arterial hypertension (PAH) is caused by adverse idiopathic remodeling of the pulmonary arteries, is ~3X more prevalent in women, and results in 5-year survival <50% due to right-ventricular (RV) failure. There are no therapies to prevent RV failure or reverse vascular remodeling in PAH. We use multi-scale experimental and computational modeling that spans from organ-scale in vivo physiology and hemodynamics to tissue-scale structural and mechanical analysis and molecular studies of cell mechano-signaling. In sugen-hypoxia rats, our in-vivo measurements and computational models show that while the male RV relies on hypertrophy to maintain compensated systolic function, female rats recruit increased myocyte contractility and hypertrophy less. While male rats developed increased filling pressures and profound myocardial matrix stiffening, female rats were protected from this fibrotic remodeling. In isolated cardiac myocytes, calcium handling had a higher functional reserve in females compared with males, and RV fibroblasts show distinct mechano-signaling responses from left-ventricular cells. These experimental and computational results suggest a new paradigm in the pathophysiology of PAH and key differences in mechanisms and outcomes between males and females.

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