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

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Дек. 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.

Язык: Английский

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Vascular mechanotransduction

Physiological Reviews, Год журнала: 2023, Номер 103(2), С. 1247 - 1421

Опубликована: Янв. 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.

Язык: Английский

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

Acta Physiologica, Год журнала: 2025, Номер 241(2)

Опубликована: Янв. 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.

Язык: 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, Год журнала: 2022, Номер 16(11), С. 19551 - 19566

Опубликована: Ноя. 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

Язык: Английский

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Extracellular Matrix in Aging Aorta

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Фев. 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.

Язык: Английский

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

Cellular and Molecular Life Sciences, Год журнала: 2023, Номер 80(6)

Опубликована: Май 10, 2023

Язык: Английский

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

Arthritis Research & Therapy, Год журнала: 2025, Номер 27(1)

Опубликована: Янв. 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.

Язык: Английский

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Extracellular vesicles in vascular remodeling

Acta Pharmacologica Sinica, Год журнала: 2022, Номер 43(9), С. 2191 - 2201

Опубликована: Янв. 12, 2022

Язык: Английский

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3D Tissue-Engineered Vascular Drug Screening Platforms: Promise and Considerations

Frontiers in Cardiovascular Medicine, Год журнала: 2022, Номер 9

Опубликована: Март 4, 2022

Despite the efforts devoted to drug discovery and development, number of new approvals have been decreasing. Specifically, cardiovascular developments showing amongst lowest levels approvals. In addition, concerns over adverse effects drugs system increasing resulting in failure at preclinical level as well withdrawal post-marketing. Besides factors such increased cost clinical trials increases requirements complexity regulatory processes, there is also a gap between currently existing pre-clinical screening methods studies humans. This mainly caused by lack used 2D cell culture-based systems, which do not accurately reflect human physiological conditions. Cell-based widely accepted extensively can provide an initial indication drugs' therapeutic efficacy potential cytotoxicity. However, vitro cell-based evaluation could many instances contradictory findings vivo testing animal models trials. drawback related these culture systems recapitulate microenvironment cells reside. body, reside within complex setting, where they interact with respond neighboring cells, extracellular matrix, mechanical stress, blood shear other factors. These sum affect cellular response specific pathways that regulate variable vital functions proliferation, apoptosis, differentiation. Although this complexity, cross species differences cause results from seen when enters Thus, need better mimic conditions improve efficiency screening. A novel approach develop 3D tissue engineered miniaturized constructs are based on cells. review, we discuss should be considered produce successful vascular construct derived both reliable reproducible.

Язык: Английский

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Role of Extracellular Vesicles as Potential Diagnostic and/or Therapeutic Biomarkers in Chronic Cardiovascular Diseases

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Янв. 26, 2022

Cardiovascular diseases (CVDs) are the first cause of death worldwide. In recent years, there has been great interest in analysis extracellular vesicles (EVs), including exosomes and microparticles, as potential mediators biological communication between circulating cells/plasma cells vasculature. Besides their activity effectors, EVs have also investigated circulating/systemic biomarkers different acute chronic CVDs. this review, role diagnostic prognostic cardiovascular diseases, atherosclerosis (mainly, peripheral arterial disease, PAD), aortic stenosis (AS) aneurysms (AAs), will be described. Mechanistically, we analyze implication pathological processes associated to remodeling, with special emphasis vascular valvular calcification. Specifically, focus on participation calcium accumulation wall valves, involving phenotypic change smooth muscle (SMCs) or interstitial (IC) osteoblast-like cells. The knowledge pathogenic mechanisms remodeling is still completely deciphered but promising results supporting translational application diagnosis therapy

Язык: Английский

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