Natalie Bienkowski
Research Mentor: Andre Monteiro Da Rocha
Mentor Department: Cardiology – CVC Cardiovascular Regeneration Core, Medicine
Author(s): Natalie Bienkowski, Julia Vallier, Alexander Visconti, Megan Randolph, Maryam Khan, Laurie Svoboda, Sasha Cai Lesher-Perez, Andre Monteiro Da Rocha
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 62
Abstract
Sex differences in cardiovascular physiology, drug response, and disease susceptibility remain appreciated, but lack mechanistic understanding. Fluctuations in sex steroid hormones including estradiol, progesterone, and testosterone are thought to impact cardiomyocyte electrophysiology and the susceptibility to environmental contamination. However, the critical need for in vitro models to recapitulate physiological changes through hormonal milieu produced by the ovarian cycle are limited due to the cycles complex and dynamic nature. Therefore, current hormone exposure in vitro don’t accurately recapitulate the ovarian cycle by the dynamic hormonal milieu, hindering the mechanistic understanding of how sex chromosomes influence cardiovascular function and environmental contaminants. Thus, isogenic human induced pluripotent stem cell-derived ventricular cardiomyocytes with different sex chromosomes (46, XX and 46, XY) derived from a patient with Klinefelter Syndrome will be cultivated. Functional syncytia- individual cells that act as a coordinated unit- will be assessed through optical mapping, where mature ventricular cardiomyocytes will be transduced with adv-GCaMO6 allowing for multiple infradian and/or ultradian assessments through longitudinal assessment of intracellular calcium transients during Microfluidic Simulated Ovarian Cycle syncytium. In addition, the assessment of the response to isoproterenol which stimulates the adrenergic system, and lead exposure will be assessed to determine any changes in susceptibility within the ovarian cycle, challenging intracellular calcium handling machinery. We hypothesize that hormonal milieu exerts a predominant role in changing cardiomyocyte electrophysiology and susceptibility to drug induced arrhythmogenesis/ environmental contaminants. This study provides a basis in developing a microfluidic based high throughput system, simulating steroid hormones that closely mimics the changes observed during the ovarian cycle, critical in modeling to study sex-dependent cardiac function.
