MechE Seminar Series

Biomechanics and Mechanobiology of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) involves adverse remodeling of pulmonary arteries, more prevalent in women, leading to a <50% 5-year survival rate due to right-ventricular (RV) failure. Current therapies can't prevent RV failure or reverse vascular remodeling. Our multi-scale approach, from in-vivo physiology to molecular studies, identified significant sex differences in tissue remodeling in sugen-hypoxia rats. Extracellular matrix remodeling in large pulmonary arteries' adventitia emerged as a major contributor to hypertension. In-vitro and computational studies revealed greater mechano-signaling responses in female pulmonary arterial adventitial fibroblasts. Male rats rely on hypertrophy for compensated systolic function, while females recruit increased myocyte contractility and hypertrophy less. Male rats develop increased filling pressures and myocardial matrix stiffening, whereas females are protected from fibrotic remodeling. Isolated cardiac myocytes in females show higher functional reserve in calcium handling than males, and RV fibroblasts exhibit distinct mechano-signaling responses. These findings suggest a novel understanding of PAH pathophysiology, emphasizing crucial differences in mechanisms and outcomes between sexes.

Pavlos P. Vlachos, Purdue University

Dr. Daniela Valdez-Jasso is an Associate Professor of Bioengineering at the University of California San Diego, where she teaches tissue biomechanics and mathematical modeling for bioengineers. She is an applied mathematician and physiologist studying the changes in the hemodynamic, mechanical, and structural properties of the pulmonary arterial vasculature and right ventricle during the progression of pulmonary arterial hypertension and the cellular mechanisms mediating extracellular remodeling in these tissues. She studies cardiac and vascular pathophysiology, soft-tissue biomechanics and mechanobiology in pulmonary arterial hypertension using her expertise in parameter estimation and optimization, uncertainty quantification, physiological systems modeling, multiscale modeling, animal models and in-vivo physiological monitoring. Her work is currently funded through the National Science Foundation CAREER: Mechanical and Structural Adaptations of Blood Vessels in Pulmonary Arterial Hypertension, the National Heart, Lung, and Blood Institute (R01) Multiscale Modeling of Right Ventricular Fibrotic Remodeling in Pulmonary Arterial Hypertension, the Wu Tsai Foundation – Human Performance Alliance, and the Conrad Prebys Foundation - Excellence in Scientific Research Leadership. Her contributions to promoting inclusion and diversity in STEM education, her outreach work with numerous campus outreach programs and student organizations were recognized with the UC San Diego Faculty Inclusive Excellence Award in 2020, and with the Institute of Engineering in Medicine GEMINI Faculty Mentor award in 2022. She is a faculty member of two NIH training grants, has numerous honors, including the Fronek Family Lectureship and Shu Chien Early Career Awards. Most recently, she has been named the UC San Diego Richard Skalak Chancellor's Endowed Faculty Fellowship in Biomedical Engineering at UC San Diego and is a Fellow of the American Heart Association. Dr. Valdez-Jasso serves in leadership positions at the American Heart Association, American Thoracic Society, and is a standing member of the Modeling and Analysis of Biological Systems (MABS) Study Session, Center for Scientific Review at the National Institutes of Health.