Sunday, May 18, 2025
5/18/2025
SHePREG: Study of Heart function in PRE-Eclampsia during and after PreGnancy - Project Summary/Abstract Advances in medicine and science have led to improved health in women, yet hypertensive disorders of pregnancy such as pre-eclampsia (PreE) remain one of the reasons that maternal cardiac disease is a leading cause of pregnancy-related death in the United States. In this project we examine the impact of severe PreE on human heart function in women from diverse racial (Non-Hispanic/Black, Non-Hispanic/White, Hispanic, South/Southeast Asian) backgrounds. We will evaluate heart function at time of delivery, and at 6- and 12- months postpartum. Our pilot data demonstrates that women with severe PreE have evidence of persistent heart dysfunction up to 3 months after delivery, and these same women display a significant number of deleterious cardiomyopathic genetic polymorphisms/DCGPs that encode for proteins implicated in cardiomyopathy. In this proposal, (Aim 1) we will describe the cardiomyopathic genetic profile of non-Hispanic Black, non-Hispanic White, Hispanic, and South/Southeast Asian women with severe PreE. Using in-silico analyses, we will characterize the pathogenicity of the identified variants in each racial cohort and determine the potential impact of the variants on peri- and post-partum heart function in each racial group. We predict that founder effect and migration may have an impact on the types of DCGPs present in each racial group, and that disease expression in the form of heart dysfunction, may be unique amongst the groups due to the social construct of race. In Aim 2 we will study the functional impact of specific DCGPs on cardiomyocyte/CM function. Using human iPSC derived CMs we will determine the impact of the mutants on kinetic function at rest and in response to stress. We will also evaluate the relationship of Ca2+ transients to CM function at rest and with stress, to determine the degree to which this may play a role in the observed contractile phenotype, a first step to link mutant status to pathogenicity. We believe that accomplishing the proposed innovative aims will significantly improve our understanding of the impact of race and genetics on heart function in women with severe PreE. This study will be the first human investigation to focus on genetic links and temporal patterns of heart function in a racially diverse cohort with severe PreE, uncovering potential new areas of investigation and future novel therapeutic pathways specific to individual race and cardiomyopathic genetic profile.
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