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Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption.
Curr Vasc Pharmacol. 2017; 15(3):265-281.CV

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.

Authors+Show Affiliations

Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Spain.Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Spain.Departamento de Morfologia e Genetica, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.Departamento de Biofísica, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Spain.Instituto Teófilo Hernando de I+D del Medicamento, Facultad de Medicina de la Universidad Autónoma de Madrid (UAM), Madrid, Spain.Departamento de Farmacologia, Escola Paulista de Medicina da Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, Brazil.Rua tres de Maio n° 100, 04044-020. Sao Paulo-SP, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28155613

Citation

Souza Bomfim, Guilherme Henrique, et al. "Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited By Chronic EtOH Consumption." Current Vascular Pharmacology, vol. 15, no. 3, 2017, pp. 265-281.
Souza Bomfim GH, Mendez-Lopez I, Arranz-Tagarro JA, et al. Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption. Curr Vasc Pharmacol. 2017;15(3):265-281.
Souza Bomfim, G. H., Mendez-Lopez, I., Arranz-Tagarro, J. A., Ferraz Carbonel, A. A., Roman-Campos, D., Padín, J. F., Garcia, A. G., Jurkiewicz, A., & Jurkiewicz, N. H. (2017). Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption. Current Vascular Pharmacology, 15(3), 265-281. https://doi.org/10.2174/1570161115666170201122750
Souza Bomfim GH, et al. Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited By Chronic EtOH Consumption. Curr Vasc Pharmacol. 2017;15(3):265-281. PubMed PMID: 28155613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional Upregulation of STIM-1/Orai-1-Mediated Store-Operated Ca2+ Contributing to the Hypertension Development Elicited by Chronic EtOH Consumption. AU - Souza Bomfim,Guilherme Henrique, AU - Mendez-Lopez,Iago, AU - Arranz-Tagarro,Juan Alberto, AU - Ferraz Carbonel,Adriana Aparecida, AU - Roman-Campos,Danilo, AU - Padín,Juan Fernando, AU - Garcia,Antonio Garcia, AU - Jurkiewicz,Aron, AU - Jurkiewicz,Neide Hyppolito, PY - 2016/05/30/received PY - 2017/01/04/revised PY - 2017/01/04/accepted PY - 2017/2/6/pubmed PY - 2017/12/13/medline PY - 2017/2/4/entrez KW - Ca2+ handling KW - STIM-1/Orai-1-mediated SOCCs activation KW - aortic remodeling KW - cardiac hypertrophy KW - chronic EtOH consumption KW - hypertension development SP - 265 EP - 281 JF - Current vascular pharmacology JO - Curr Vasc Pharmacol VL - 15 IS - 3 N2 - 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. SN - 1875-6212 UR - https://www.unboundmedicine.com/medline/citation/28155613/Functional_Upregulation_of_STIM_1/Orai_1_Mediated_Store_Operated_Ca2+_Contributing_to_the_Hypertension_Development_Elicited_by_Chronic_EtOH_Consumption_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1570-1611&volume=15&issue=3&spage=265&aulast=Souza Bomfim DB - PRIME DP - Unbound Medicine ER -