Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption

Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption

Author Bomfim, Guilherme Henrique Souza Autor UNIFESP Google Scholar
Mendez-Lopez, Iago Google Scholar
Alberto Arranz-Tagarro, Juan Google Scholar
Carbonel, Adriana Aparecida Ferraz Autor UNIFESP Google Scholar
Roman-Campos, Danilo Autor UNIFESP Google Scholar
Fernando Padin, Juan Google Scholar
Garcia Garcia, Antonio Google Scholar
Jurkiewicz, Aron Autor UNIFESP Google Scholar
Jurkiewicz, Neide Hyppolito Autor UNIFESP Google Scholar
Abstract Background: Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca2+) handling. Store-operated Ca2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM-1 (ER Ca2+ sensor) and Orai-1 (channel pore) is a key mechanism to control SOCE through of store-operated Ca2+ channels (SOCCs). However, the role of STIM-1/Orai-1-mediated SOCE and its cross-talk with EtOH-triggered vascular remodeling and hypertension remain poorly understood. We address this subject in the present study by evaluating how chronic EtOH consumption induces alterations in Ca2+ handling via SOCE. Methods: Male Wistar Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days). Systolic blood pressure (SBP) and EtOH concentration were measured

cardiovascular remodeling was assessed by histomorphometry

and function/expression of STIM-1/Orai-1-mediated Ca2+ influx were evaluated by isometric contraction and western blot experiments. Results: Compared to the WKY-Control, our results show that: (1) chronic EtOH consumption caused a significant elevation of SBP in both strains

(2) cardiac hypertrophy and hypertrophic aortic wall remodeling much more pronounced in WKY-EtOH

(3) decreased capacity of ER to store and release Ca2+

(4) increased STIM-1/Orai-1-mediated SOCCs activation, which was selectively inhibited by YM-58483

and (5) increased expression of STIM-1 in WKY-EtOH and SHR-Control rats. Conclusion: These findings suggest that hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca2+ overload via STIM-1/Orai-1-mediated SOCE through SOCCs are involved hypertension developed by EtOH consumption.
Keywords Ca2+ handling
STIM-1/Orai-1-mediated SOCCs activation
cardiac hypertrophy
aortic remodeling
chronic EtOH consumption
hypertension development
xmlui.dri2xhtml.METS-1.0.item-coverage Sharjah
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Ministerio de Economia y Competitividad, Espana
Grant number CAPES: BEX 8477/13-2
FAPESP: 2014/01569-0
Ministerio de Economia y Competitividad, Espana: SAF: 2013-44108-P, FPI BES-2014-069005
Date 2017
Published in Current Vascular Pharmacology. Sharjah, v. 15, n. 3, p. 265-281, 2017.
ISSN 1570-1611 (Sherpa/Romeo, impact factor)
Publisher Bentham Science Publ Ltd
Extent 265-281
Access rights Closed access
Type Article
Web of Science ID WOS:000399595500009

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