Stress Matters: Engineering In Vitro Models of Sex Specific Cardiac Biomechanics
Heart failure (HF) is an expanding health problem worldwide that affects >64 M people across the globe. Although heart HF affects both women and men, data suggest that HF pathogenesis differs between sexes. Indeed, women have smaller and stiffer left-ventricles (LV) with increased cardiac fibrosis at old age and higher ejection fraction than men. Women with HF survive longer than men and have lower risk of sudden death. However, women are frequently overlooked by routine exams and less adequately treated since most therapeutics were derived from predominantly male-population studies. Moreover, hormones can lead to sex differences in the cardiac excitation-contraction coupling pathway, thus affecting the biomechanics of the heart in a sex-specific fashion (e.g., estrogen may increase susceptibility to rhythm disorders). Studies have shown that pathological mechanical stress is a major driver of fibrosis and can promote progression of HF; however there is limited understanding of the biological mechanisms and effects of sex-differences on cardiac biomechanics, particularly how this affects women’s health. We have engineered different tools to study the effects of mechanical stresses on cells which can recapitulate cardiac forces and injury, such as tension and compressional stresses that occur during cardiac damage and recovery (e.g. exercise or HF). Our goal is to provide tools to elucidate the effects of mechanical stresses on sex-specific cardiac cells, and to identify sex-specific molecular mechanisms that trigger fibrosis in the heart to further engineer precise therapeutics for both women and men.
Speaker
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Brisa Peña CastellanosUniversity of Colorado, Anschutz Medical Campus, USADr. Peña is a Chemical Engineer and a Polymer and Material Scientist with specific training in cardiovascular and bioengineering research. She obtained her master and PhD from the Univerity Rovira i Virgili, in Tarragona Spain. She did her postdoctoral training here in the Bioengineering Department and in the Division of Cardiology, and as well as in the University of Trieste and in the International Centre for Genetic Engineering and Biotechnology I.C.G.E.B in Trieste Italy. She is currently an Assistant Professor in the Bioengineering Department and in the Division of Cardiology at the University of Colorado Denver | Anschutz Medical Campus. She is funded a National Institutes of Health (NIH) K25 career development award from the National Heart, Lung, and Blood Institute (NHLBI) (2020- 2025), a R21 from the National Institute on Aging (NIA) (collaborator) (2023-2025), and R01 from the NHLBI (Co-investigator) (2023- 2025), an American Heart Association Career Development award (2023 – 2026) and most recently a collaborative seed grant from the Ludeman Family Center for Women’s Health Research.
Dr. Peña has vast experience in the biophysical and biomechanical analysis of tissues and living cells using atomic force microscopy (AFM). In addition, she has specific experience in translational research using biomaterials, nanotechnology and cell biology for cardiac tissue engineering. As a result, and together with her collaborators, her group has engineered biomaterials for cardiovascular tissue engineering and medical devices for which they have submitted four patent applications, three of them already granted. Her current and future research goals are committed to focus on sex as a biological variable to dissect mechanobiological mechanisms governing sex-related differences in the heart. She is particularly interested to study the effect of mechanical stresses on sex-specific cardiac cells using engineered mechanical devices designed in her lab (provisional patent granted) and its application to further engineer precise sex-specific therapeutics that target heart failure.