Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway.

Scientific Reports
P ReventunM Saura

Abstract

Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bi...Continue Reading

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Citations

Nov 13, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Liyuan Cao, Wei Mu
Apr 2, 2021·International Journal of Cardiology·Ampadu O JacksonShiyin Long
Apr 11, 2021·Journal of Biomedical Science·Chanon PiamsiriNipon Chattipakorn
Jun 19, 2021·Frontiers in Molecular Biosciences·Yingjie YangYaozu Xiang
Aug 5, 2021·Environmental Science and Pollution Research International·Ting YinHaifeng Zhang
Aug 7, 2021·Biomolecules·Rafael Moreno-Gómez-ToledanoRicardo J Bosch
Aug 22, 2021·Environmental Research·Christopher J MartyniukLorraine Chalifour

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
electrophoresis
FACS
RIP

Software Mentioned

Spike
Cyflogic

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