Functional Upregulation of STIM‐1/Orai‐1‐Mediated Store‐Operated Ca 2+ Entry Contributing to the Aortic Remodeling and Hypertension Development by Chronic EtOH Consumption
Abstract only Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca 2+ ) handling. Store‐operated Ca 2+ entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling be...
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| Published in: | The FASEB journal Vol. 31; no. S1 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
01-04-2017
|
| Online Access: | Get full text |
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| Summary: | Abstract only
Chronic ethanol (EtOH) consumption has been associated with deleterious effects on the cardiovascular system by abnormal calcium (Ca
2+
) handling. Store‐operated Ca
2+
entry (SOCE) is related to cardiovascular remodeling which leads to the hypertension development, and the coupling between STIM‐1 (Ca
2+
sensor) and Orai‐1 (channel pore) is a key mechanism to control SOCE through of store‐operated Ca
2+
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 Ca
2+
handling via SOCE. 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 Ca
2+
influx were evaluated by isometric contraction and western blot experiments. 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 reticulum to store and release Ca
2+
; (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. These findings suggest that hypertension developed by EtOH consumption has as one of its origins the hypertrophic aortic remodeling and abnormal contraction triggered mainly by Ca
2+
overload via STIM‐1/Orai‐1‐mediated SOCE through SOCCs.
Support or Funding Information
This work was supported by the Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior‐CAPES (BEX 8477/13‐2); the Fundação de Amparo a Pesquisa do Estado de São Paulo‐FAPESP (2014/01569‐0); the Ministerio de Economía y Competitividad, España (SAF: 2013‐44108‐P and FPI BES‐2014‐069005). |
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| ISSN: | 0892-6638 1530-6860 |
| DOI: | 10.1096/fasebj.31.1_supplement.672.6 |