Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence.

Autor: Yang W; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Lu C; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Chu F; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Bu K; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Ma H; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Wang Q; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China; Teaching Center of Morphology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China., Jiao Z; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China; Institute for Kashin Beck Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, China., Wang S; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Yang X; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Gao Y; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Sun D; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China., Sun H; Institute for Endemic Fluorosis Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University) Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), China. Electronic address: hrbmushn@hrbmu.edu.cn.
Jazyk: angličtina
Zdroj: Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2024 Aug; Vol. 281, pp. 116681. Date of Electronic Publication: 2024 Jul 04.
DOI: 10.1016/j.ecoenv.2024.116681
Abstrakt: Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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