Saravanakumar Murugesan, Lakshmi Saravanakumar, Sakthivel Sadayappan, Ramaswamy Kannappan, Rachel G Sinkey, Michelle D Tubinis, Alan N Tita, Tamas Jilling, Dan E Berkowitz
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引用次数: 0
Abstract
Women with severe preeclampsia (sPE) exhibit a heightened risk of postpartum cardiovascular disease compared to those with normotensive pregnancies (NTP). While placental extracellular vesicles (EV) play a crucial role in feto-maternal communication, their impact on cardiomyocytes, particularly in the context of sPE, remains unclear. This study investigated the effect of sPE-associated placental EV (sPE-Plex EV) on cardiomyocyte calcium dynamics. We hypothesized that sPE-Plex EV mediates cardiomyocyte dysfunction by disrupting calcium signaling. EV were isolated from plasma and placental explant culture (Plex) using precipitation methods, and confirmed as Plex EV by PLAP activity and electron microscopy. Moreover, confocal microscopy confirmed the uptake of plasma EV in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and Plex EV by human AC-16 cardiomyocytes (hAC-16CM) cells. hiPSC-CM cells treated with sPE-EV and hAC-16CM cells treated with sPE-Plex EV exhibited significantly lower levels of Stromal interaction molecule 1 (STIM1) and Phospholamban (PLN) proteins compared to those treated with normotensive controls EV, as confirmed by western blot analysis. Treatment with sPE-Plex EV also resulted in the downregulation of STIM1 and PLN proteins in murine cardiomyocyte (mCM) cells compared to treatment with NTP-Plex EV. Our findings suggest that both plasma EV and Plex EV from sPE may alter calcium signaling in cardiac cells by downregulating calcium sensor proteins (STIM1 and PLN). Therefore, plasma EV and Plex EV from sPE pregnancies have adverse effects by altering calcium dynamics in hiPSC-CM, hAC-16CM, and mCM compared to normotensive control and potential impairment of cardiomyocyte function ex vivo.
期刊介绍:
The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.