Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(9), С. 7910 - 7910

Опубликована: Апрель 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Язык: Английский

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Endothelial Dysfunction: Redox Imbalance, NLRP3 Inflammasome, and Inflammatory Responses in Cardiovascular Diseases

Antioxidants, Год журнала: 2025, Номер 14(3), С. 256 - 256

Опубликована: Фев. 23, 2025

Endothelial dysfunction (ED) is characterized by an imbalance between vasodilatory and vasoconstrictive factors, leading to impaired vascular tone, thrombosis, inflammation. These processes are critical in the development of cardiovascular diseases (CVDs) such as atherosclerosis, hypertension ischemia/reperfusion injury (IRI). Reduced nitric oxide (NO) production increased oxidative stress key contributors ED. Aging further exacerbates ED through mitochondrial oxidative/nitrosative stress, heightening CVD risk. Antioxidant systems like superoxide-dismutase (SOD), glutathione-peroxidase (GPx), thioredoxin/thioredoxin-reductase (Trx/TXNRD) pathways protect against stress. However, their reduced activity promotes ED, vulnerability IRI. Metabolic syndrome, comprising insulin resistance, obesity, hypertension, often accompanied Specifically, hyperglycemia worsens endothelial damage promoting Obesity leads chronic inflammation changes perivascular adipose tissue, while associated with increase The NLRP3 inflammasome plays a significant role being triggered factors reactive oxygen nitrogen species, ischemia, high glucose, which contribute inflammation, injury, exacerbation Treatments, N-acetyl-L-cysteine, SGLT2 or inhibitors, show promise improving function. Yet complexity suggests that multi-targeted therapies addressing metabolic disturbances essential for managing CVDs syndrome.

Язык: Английский

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Molecular Determinants of Chronic Venous Disease: A Comprehensive Review

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 1928 - 1928

Опубликована: Янв. 18, 2023

Chronic Venous Disease (CVD) refers to several pathological and hemodynamic alterations of the veins lower limbs causing a wide range symptoms signs with high prevalence in general population disabling consequences most severe forms. The etiology pathophysiology CVD is complex multifactorial, involving genetic, proteomic, cellular mechanisms that result changes venous structure functions. Expressions genes associated angiogenesis, vascular development, regulation are responsible for susceptibility CVD. Current evidence shows extracellular matrix (ECM) could be identified some cases pharmacologically targeted. This review up date information on molecular determinants order provide complete overview current knowledge this topic. In particular, article explores genetic influence, hormonal ECM imbalance, histopathology role endothelial dysfunction

Язык: Английский

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Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines

Annals of Intensive Care, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 24, 2024

Maintaining tissue perfusion in sepsis depends on vascular integrity provided by the endothelial glycocalyx, critical layer covering luminal surface of blood vessels. The glycocalyx is composed proteoglycans, glycosaminoglycans, and functional plasma proteins that are for antithrombogenicity, regulating tone, controlling permeability, reducing interactions with leukocytes platelets. Degradation substantial due to thromboinflammation, treatments septic shock may exacerbate endotheliopathy via additional injury. As a result, therapeutic strategies aimed at preserving should be considered, including modifications fluid volume resuscitation, minimizing catecholamine use, hyperglycemia, potential use corticosteroids anticoagulants. In this review, we explore treatment aligned recommendations outlined Surviving Sepsis Campaign Guidelines 2021 special emphasis evidence regarding protection.

Язык: Английский

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Basal endothelial glycocalyx’s response to shear stress: a review of structure, function, and clinical implications

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 18, 2024

The endothelial glycocalyx encompasses the entire cell, transducing extracellular signals and regulating vascular permeability barrier functions. apical glycocalyx, which forms lumen of vessel, basal at smooth muscle cell interface, are often investigated separately as they exposed to vastly different stimuli. directly senses fluid shear forces transmitting them intracellularly through connection cytoskeleton cell. has demonstrated sensitivity due blood flow transmitted cytoskeleton, promoting alternate signaling processes. In this review, we discuss current literature on glycocalyx’s response stress in context mechanotransduction remodeling. possible implications degradation pathologies also explored. Finally, review seeks highlight how addressing gaps discussed would improve our wholistic understanding its role maintaining homeostasis.

Язык: Английский

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Blood–brain barrier alterations and their impact on Parkinson’s disease pathogenesis and therapy

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Июль 29, 2024

There is increasing evidence for blood-brain barrier (BBB) alterations in Parkinson's disease (PD), the second most common neurodegenerative disorder with rapidly rising prevalence. Altered tight junction and transporter protein levels, accumulation of α-synuclein increase inflammatory processes lead to extravasation blood molecules vessel degeneration. This could result a self-perpetuating pathophysiology inflammation BBB alteration, which contribute neurodegeneration. Toxin exposure or over-expression animal models has been shown initiate similar pathologies, providing platform study underlying mechanisms therapeutic interventions. Here we provide comprehensive review current knowledge on PD patients how rodent that replicate some these changes can be used mechanisms. Specific challenges assessing healthy controls are discussed. Finally, potential role pathogenesis possible implications therapy explored. The interference novel strategies requires more attention. Brain region-specific also open up opportunities target specifically vulnerable neuronal subpopulations.

Язык: Английский

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Extracellular matrix in vascular homeostasis and disease

Nature Reviews Cardiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Язык: Английский

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A Narrative Review: Syndecans in Aortic Aneurysm Pathogenesis and Course—Biomarkers and Targets?

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1211 - 1211

Опубликована: Янв. 30, 2025

The maintenance of the integrity entire endothelium, glycocalyx included, and, therefore, tissue aorta’s homeostasis, depends on expressions several molecular pathways and their interactions, such as syndecan molecules. Alterations in syndecans, i.e., quantitative alterations or linking to shedding, contributes invoking endothelium dysfunction, which causes damage vessel wall due increased production growth-stimulating pro-inflammatory gene products. Inflammatory processes negatively affect endothelial glycocalyx, a dynamic layer luminal portion cells composed proteoglycans, glycoproteins, glycosaminoglycans, syndecans. In turn, structural influence coagulative state, increasing pro-thrombotic processes. family syndecans constitutes major component or, more accurately, source cell surface heparan sulfate. It encompasses four components: syndecan-1, syndecan-2, syndecan-4 (with syndecan-3 only expressed neural tissue), have fundamental role regulating events acute chronic aorta subsequently correlated with formation aneurysms. As such, aim our review is highlight current knowledge roles analyze relationship pathological aortic based most recent literature.

Язык: Английский

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From immune dysregulation to organ dysfunction: understanding the enigma of Sepsis

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Авг. 26, 2024

Sepsis is a syndrome precipitated by immune dysregulation in response to infection, and represents pivotal factor global mortality attributed diseases. The recent consensus delineates sepsis as perilous state of organ dysfunction arising from the host’s maladaptive reaction infection. It masks complexity breadth mechanisms involved sepsis, which characterized simultaneous hyperinflammation immunosuppression. highly correlated with response, mainly mediated various cells their interactions. This can lead plethora complications, encompassing systemic inflammatory metabolic disturbances, infectious shock, MODS, DIC. Furthermore, more research studies have been conducted on past few years. pathological characteristics improved or treated targeting signaling pathways like NF-B, JAK–STAT, PI3K-Akt, p38-MAPK. Combined drug therapy better than single for sepsis. article will review latest progress pathogenesis treatment

Язык: Английский

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ECM Microenvironment in Vascular Homeostasis: New Targets for Atherosclerosis

Physiology, Год журнала: 2024, Номер 39(5), С. 324 - 344

Опубликована: Июль 10, 2024

Alterations in vascular extracellular matrix (ECM) components, interactions, and mechanical properties influence both the formation stability of atherosclerotic plaques. This review discusses contribution ECM microenvironment homeostasis remodeling atherosclerosis, highlighting Cartilage oligomeric protein (COMP) its degrading enzyme ADAMTS7 as examples, proposes potential avenues for future research aimed at identifying novel therapeutic targets atherosclerosis based on microenvironment.

Язык: Английский

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