Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review

Abstract Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate memb...

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Main Authors: Yoshiaki Suzuki, Wayne R. Giles, Gerald W. Zamponi, Rubii Kondo, Yuji Imaizumi, Hisao Yamamura
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Inflammation and Regeneration
Subjects:
Online Access:https://doi.org/10.1186/s41232-024-00363-0
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author Yoshiaki Suzuki
Wayne R. Giles
Gerald W. Zamponi
Rubii Kondo
Yuji Imaizumi
Hisao Yamamura
author_facet Yoshiaki Suzuki
Wayne R. Giles
Gerald W. Zamponi
Rubii Kondo
Yuji Imaizumi
Hisao Yamamura
author_sort Yoshiaki Suzuki
collection DOAJ
description Abstract Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca2+ concentration ([Ca2+]cyt) in response to such stimuli. The subsets of these ion channels involved in Ca2+ signaling often form molecular complexes with intracellular molecules via scaffolding proteins. This allows Ca2+ signaling to be tightly controlled in localized areas within the cell, resulting in a balanced vascular tone. When hypertensive stimuli are applied to blood vessels for extended periods, gene expression in these vascular cells can change dramatically. For example, alteration in ion channel expression often induces electrical remodeling that produces a depolarization of the membrane potential and elevated [Ca2+]cyt. Coupled with endothelial dysfunction blood vessels undergo functional remodeling characterized by enhanced vasoconstriction. In addition, pathological challenges to vascular cells can induce inflammatory gene products that may promote leukocyte infiltration, in part through Ca2+-dependent pathways. Macrophages accumulating in the vascular adventitia promote fibrosis through extracellular matrix turnover, and cause structural remodeling of blood vessels. This functional and structural remodeling often leads to chronic hypertension affecting not only blood vessels, but also multiple organs including the brain, kidneys, and heart, thus increasing the risk of severe cardiovascular events. In this review, we outline recent advances in multidisciplinary research concerning Ca2+ signaling in VSMCs and ECs, with an emphasis on the mechanisms underlying functional and structural vascular remodeling.
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spelling doaj-art-62ec1e6ba73b4137978a699efc31b3cc2025-08-20T02:39:34ZengBMCInflammation and Regeneration1880-81902024-12-0144111410.1186/s41232-024-00363-0Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a reviewYoshiaki Suzuki0Wayne R. Giles1Gerald W. Zamponi2Rubii Kondo3Yuji Imaizumi4Hisao Yamamura5Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityDepartment of Physiology & Pharmacology, Cumming School of Medicine, University of CalgaryDepartment of Clinical Neurosciences, Hotchkiss Brain Institute, Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of CalgaryDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityDepartment of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City UniversityAbstract Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca2+ concentration ([Ca2+]cyt) in response to such stimuli. The subsets of these ion channels involved in Ca2+ signaling often form molecular complexes with intracellular molecules via scaffolding proteins. This allows Ca2+ signaling to be tightly controlled in localized areas within the cell, resulting in a balanced vascular tone. When hypertensive stimuli are applied to blood vessels for extended periods, gene expression in these vascular cells can change dramatically. For example, alteration in ion channel expression often induces electrical remodeling that produces a depolarization of the membrane potential and elevated [Ca2+]cyt. Coupled with endothelial dysfunction blood vessels undergo functional remodeling characterized by enhanced vasoconstriction. In addition, pathological challenges to vascular cells can induce inflammatory gene products that may promote leukocyte infiltration, in part through Ca2+-dependent pathways. Macrophages accumulating in the vascular adventitia promote fibrosis through extracellular matrix turnover, and cause structural remodeling of blood vessels. This functional and structural remodeling often leads to chronic hypertension affecting not only blood vessels, but also multiple organs including the brain, kidneys, and heart, thus increasing the risk of severe cardiovascular events. In this review, we outline recent advances in multidisciplinary research concerning Ca2+ signaling in VSMCs and ECs, with an emphasis on the mechanisms underlying functional and structural vascular remodeling.https://doi.org/10.1186/s41232-024-00363-0Ca2+ signalingEndothelial cellsHypertensionMacrophagesMonocytesVascular remodeling
spellingShingle Yoshiaki Suzuki
Wayne R. Giles
Gerald W. Zamponi
Rubii Kondo
Yuji Imaizumi
Hisao Yamamura
Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
Inflammation and Regeneration
Ca2+ signaling
Endothelial cells
Hypertension
Macrophages
Monocytes
Vascular remodeling
title Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
title_full Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
title_fullStr Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
title_full_unstemmed Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
title_short Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review
title_sort ca2 signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling a review
topic Ca2+ signaling
Endothelial cells
Hypertension
Macrophages
Monocytes
Vascular remodeling
url https://doi.org/10.1186/s41232-024-00363-0
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