Vascular mechanotransduction

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(2), P. 1247 - 1421

Published: Jan. 5, 2023

This review aims to survey the current state of mechanotransduction in vascular smooth muscle cells (VSMCs) and endothelial (ECs), including their sensing mechanical stimuli transduction signals that result acute functional modulation longer-term transcriptomic epigenetic regulation blood vessels. The mechanosensors discussed include ion channels, plasma membrane-associated structures receptors, junction proteins. mechanosignaling pathways presented cytoskeleton, integrins, extracellular matrix, intracellular signaling molecules. These are followed by discussions on transcriptome epigenetics, relevance health disease, interactions between VSMCs ECs. Throughout this review, we offer suggestions for specific topics require further understanding. In closing section conclusions perspectives, summarize what is known point out need treat vasculature as a system, not only ECs but also matrix other types such resident macrophages pericytes, so can fully understand physiology pathophysiology vessel whole, thus enhancing comprehension, diagnosis, treatment, prevention diseases.

Language: Английский

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Dysfunctional Vascular Endothelium as a Driver of Atherosclerosis: Emerging Insights Into Pathogenesis and Treatment

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 22, 2021

Atherosclerosis, the chronic accumulation of cholesterol-rich plaque within arteries, is associated with a broad spectrum cardiovascular diseases including myocardial infarction, aortic aneurysm, peripheral vascular disease, and stroke. Atherosclerotic disease remains leading cause mortality in high-income countries recent years have witnessed notable increase prevalence low- middle-income regions world. Considering this prominent evolving global burden, there need to identify cellular mechanisms that underlie pathogenesis atherosclerosis discover novel therapeutic targets for preventing or mitigating its clinical sequelae. Despite decades research, we still do not fully understand complex cell-cell interactions drive atherosclerosis, but new investigative approaches are rapidly shedding light on these essential mechanisms. The endothelium resides at interface systemic circulation underlying vessel wall plays an role governing pathophysiological processes during atherogenesis. In review, present emerging evidence implicates activated as driver by directing site-specificity formation promoting development through intracellular processes, which regulate endothelial cell proliferation turnover, metabolism, permeability, plasticity. Moreover, highlight intercellular communication cells modulate activity key populations involved atherogenesis, discuss how contribute resolution biology - process dysregulated advanced plaques. Finally, describe important future directions preclinical epigenetic targeted therapies, limit progression at-risk affected patients.

Language: Английский

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Transient receptor potential melastatin 7 cation channel, magnesium and cell metabolism in vascular health and disease

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 12, 2025

Abstract Preserving the balance of metabolic processes in endothelial cells (ECs) and vascular smooth muscle (VSMCs), is crucial for optimal function integrity. ECs are metabolically active depend on aerobic glycolysis to efficiently produce energy their essential functions, which include regulating tone. Impaired EC metabolism linked damage, increased permeability inflammation. Metabolic alterations VSMCs also contribute dysfunction atherosclerosis hypertension. Magnesium (Mg 2+ ) second most abundant intracellular divalent cation influences molecular that regulate function, including vasodilation, vasoconstriction, release vasoactive substances. Mg critically involved maintaining cellular homeostasis since it an cofactor ATP, nucleic acids hundreds enzymes processes. Low levels have been dysfunction, tone, inflammation arterial remodeling. Growing evidence indicates important role transient receptor potential melastatin‐subfamily member 7 (TRPM7) channel regulation VSMCs. In vasculature, TRPM7 deficiency leads impaired contraction, phenotypic switching VSMCs, fibrosis, characterize phenotype Here we provide a comprehensive overview TRPM7/Mg how VSMC such as glucose homeostasis, redox regulation, phosphoinositide signaling, mineral metabolism. The putative altered hypertension discussed.

Language: Английский

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Rescuing Cardiac Cells and Improving Cardiac Function by Targeted Delivery of Oxygen-Releasing Nanoparticles after or Even before Acute Myocardial Infarction

ACS Nano, Journal Year: 2022, Volume and Issue: 16(11), P. 19551 - 19566

Published: Nov. 11, 2022

Myocardial infarction (MI) causes massive cell death due to restricted blood flow and oxygen deficiency. Rapid sustained delivery following MI rescues cardiac cells restores function. However, current oxygen-generating materials cannot be administered during acute stage without direct injection or suturing methods, both of which risk rupturing weakened heart tissue. Here, we present infarcted heart-targeting, oxygen-releasing nanoparticles capable being delivered by intravenous at stage, specifically accumulating in the heart. The can also before MI, then gather injured area after MI. We demonstrate that nanoparticles, either pre-MI post-MI, enhance survival, stimulate angiogenesis, suppress fibrosis inducing substantial inflammation reactive species overproduction. Our findings oxygen-delivering provide a nonpharmacological solution rescue preserve

Language: Английский

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Extracellular Matrix in Aging Aorta

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Feb. 21, 2022

The aging population is booming all over the world and arterial causes various age-associated pathologies such as cardiovascular diseases (CVDs). aorta largest elastic artery, transforms pulsatile flow generated by left ventricle into steady to maintain circulation in distal tissues organs. Age-associated structural functional changes aortic wall dilation, tortuousness, stiffening losing elasticity hamper stable peripheral circulation, lead tissue organ dysfunctions aged people. extracellular matrix (ECM) a three-dimensional network of macromolecules produced resident cells. composition organization key ECM components determine structure-function relationships therefore maintaining their homeostasis critical for healthy performance. remodeling components, including fragmentation fibers excessive deposition crosslinking collagens, hallmark leads aorta. In this mini review, we discuss alterations shed light on how understanding mechanisms can development efficient strategy CVDs.

Language: Английский

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MicroRNA regulation of phenotypic transformations in vascular smooth muscle: relevance to vascular remodeling

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(6)

Published: May 10, 2023

Language: Английский

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Exosome miR-199a-5p modulated vascular remodeling and inflammatory infiltration of Takayasu’s arteritis

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: Jan. 20, 2025

Advances in treatment have swiftly alleviated systemic inflammation of Takayasu's arteritis (TAK), while subclinical vascular and the ensuing arterial remodeling continue to present unresolved challenges TAK. The phenotypic switching smooth muscle cells (VSMC) is regarded as first step pathology contributes remodeling. Exosomes facilitate transfer exchange proteins specific nucleic acids, thereby playing a significant role intercellular communication. Little known about modulatory serum exosomes VSMC Serum isolated from TAK patients were co-cultured with identify exosomes. transfected miR-199a-5p mimic inhibitor. CCK8 assays EdU performed measure proliferative ability. migration was evaluated by scratch transwell assays. flow cytometry employed apoptosis VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay fluorescence situ hybridization utilized validate target gene miR-199a-5p. correlational analysis conducted among exosome miRNA, MMP2, TIMP2 clinical parameters patients. coculture mediated dedifferentiation Through gain- loss-of-function approaches, over-expression significantly increased expression marker genes inhibited proliferation migration, whilst opposite effect observed when endogenous knocked down. overexpression suppressed apoptosis. Further, MMP2 serves functional correlation analyses revealed an inverse between Vasculitis Damage Index level or which requires validation larger cohort. Our study indicated that miR-199a-5p/MMP2 pathway played inhibiting decreased secretion may potentially prompt intimal infiltration inflammatory within wall, offering novel therapeutic opportunity tackling both responses neointimal overgrowth associated damage. Moreover, derived possess potential future biomarkers for injury.

Language: Английский

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Functions and application of circRNAs in vascular aging and aging-related vascular diseases

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 17, 2025

Circular RNAs (circRNAs), constituting a novel class of endogenous non-coding generated through the reverse splicing mRNA precursors, possess capacity to regulate gene transcription and translation. Recently, pivotal role circRNAs in controlling vascular aging, as well pathogenesis progression aging-related diseases, has garnered substantial attention. Vascular aging plays crucial increased morbidity mortality elderly. Endothelial cells (ECs) smooth muscle (VSMCs) are components intima media layers wall, respectively, closely involved mechanisms underlying diseases. The review aims provide comprehensive exploration connection between Besides, circRNAs, potential diagnostic markers or therapeutic targets for will be discussed thoroughly, along with challenges limitations their clinical application. Investigating molecular diseases insight into early diagnosis therapy, even effective prognosis assessment these conditions.

Language: Английский

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The Atherosclerotic Plaque Microenvironment as a Therapeutic Target

Current Atherosclerosis Reports, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 2, 2025

Atherosclerosis is traditionally viewed as a disease triggered by lipid accumulation, but growing evidence underscores the crucial role of plaque microenvironment in progression. This review explores recent advances understanding how cellular and extracellular components milieu drive atherosclerosis, with focus on leveraging these microenvironmental factors for therapeutic intervention. highlights cell-cell crosstalk matrix remodeling, offering insights into innovative strategies atherosclerotic cardiovascular disease. While atherosclerosis begins subendothelial retention apolipoprotein B (ApoB)-containing lipoproteins​, its progression increasingly recognized consequence complex dynamics within microenvironment. Soluble proteins shape mechanical properties biochemical landscape, directly influencing cell behavior inflammatory signaling. For instance, deposition transitional proteins, such fibronectin, regions disturbed flow primes endothelial cells inflammation​. Likewise, impaired clearance dead chronic remodeling contribute to lesion expansion instability, further exacerbating severity. Targeting presents promising avenue stabilizing lesions. Approaches that enhance beneficial interactions, boosting macrophage efferocytosis resolve inflammation while mitigating proatherogenic signals like integrin-mediated activation, may promote fibrous cap formation reduce vulnerability. Harnessing mechanisms lead novel approaches aimed at modifying combat

Language: Английский

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Extracellular vesicles in vascular remodeling

Acta Pharmacologica Sinica, Journal Year: 2022, Volume and Issue: 43(9), P. 2191 - 2201

Published: Jan. 12, 2022

Language: Английский

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