Oxidative Stress and Hypertension

Circulation Research, Год журнала: 2021, Номер 128(7), С. 993 - 1020

Опубликована: Апрель 1, 2021

A link between oxidative stress and hypertension has been firmly established in multiple animal models of but remains elusive humans. While initial studies focused on inactivation nitric oxide by superoxide, our understanding relevant reactive oxygen species (superoxide, hydrogen peroxide, peroxynitrite) how they modify complex signaling pathways to promote expanded significantly. In this review, we summarize recent advances delineating the primary secondary sources (nicotinamide adenine dinucleotide phosphate oxidases, uncoupled endothelial synthase, endoplasmic reticulum, mitochondria), posttranslational modifications induce protein targets important for redox signaling, their interplay with endogenous antioxidant systems, role inflammasome activation reticular development hypertension. We highlight different organ systems contributes hypertension, describe new that have clarified importance specific proteins, discuss clinical shed light these processes are altered human Finally, focus promise proteomics biology help us fully understand relationship ROS potential designing evaluating novel antihypertensive therapies.

Язык: Английский

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Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications

Physiological Reviews, Год журнала: 2021, Номер 101(4), С. 1745 - 1807

Опубликована: Май 5, 2021

The prevalence of heart failure is on the rise and imposes a major health threat, in part, due to rapidly increased overweight obesity. To this point, epidemiological, clinical, experimental evidence supports existence unique disease entity termed "obesity cardiomyopathy," which develops independent hypertension, coronary disease, other diseases. Our contemporary review evaluates for pathological condition, examines putative responsible mechanisms, discusses therapeutic options disorder. Clinical findings have consolidated presence left ventricular dysfunction Experimental investigations uncovered pathophysiological changes myocardial structure function genetically predisposed diet-induced Indeed, consolidates wide array cellular molecular mechanisms underlying etiology obesity cardiomyopathy including adipose tissue dysfunction, systemic inflammation, metabolic disturbances (insulin resistance, abnormal glucose transport, spillover free fatty acids, lipotoxicity, amino acid derangement), altered intracellular especially mitochondrial Ca2+ homeostasis, oxidative stress, autophagy/mitophagy defect, fibrosis, dampened flow reserve, microvascular (microangiopathy), endothelial impairment. Given important role risk failure, that with preserved systolic recent rises COVID-19-associated cardiovascular mortality, should provide compelling cardiomyopathy, various comorbid conditions, offer new insights into potential approaches (pharmacological lifestyle modification) clinical management cardiomyopathy.

Язык: Английский

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Targeting autophagy in ischemic stroke: From molecular mechanisms to clinical therapeutics

Pharmacology & Therapeutics, Год журнала: 2021, Номер 225, С. 107848 - 107848

Опубликована: Апрель 4, 2021

Язык: Английский

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Endoplasmic reticulum stress in liver diseases

Hepatology, Год журнала: 2022, Номер 77(2), С. 619 - 639

Опубликована: Май 7, 2022

The endoplasmic reticulum (ER) is an intracellular organelle that fosters the correct folding of linear polypeptides and proteins, a process tightly governed by ER‐resident enzymes chaperones. Failure to shape proper 3‐dimensional architecture proteins culminates in accumulation misfolded or unfolded within ER, disturbs ER homeostasis, leads canonically defined stress. Recent studies have elucidated cellular perturbations, such as lipotoxicity, can also lead In response stress, protein (UPR) activated reestablish homeostasis (“adaptive UPR”), or, conversely, provoke cell death when stress overwhelmed sustained (“maladaptive UPR”). It well documented contributes onset progression multiple hepatic pathologies including NAFLD, alcohol‐associated liver disease, viral hepatitis, ischemia, drug toxicity, cancers. Here, we review key dealing with emerging role UPR pathophysiology diseases from cellular, murine, human models. Specifically, will summarize current available knowledge on pharmacological non‐pharmacological interventions may be used target maladaptive for treatment nonmalignant diseases.

Язык: Английский

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Endoplasmic reticulum stress-mediated cell death in liver injury

Cell Death and Disease, Год журнала: 2022, Номер 13(12)

Опубликована: Дек. 19, 2022

The endoplasmic reticulum is an important intracellular organelle that plays role in maintaining cellular homeostasis. Endoplasmic stress (ERS) and unfolded protein response (UPR) are induced when the body exposed to adverse external stimuli. It has been established ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, pyroptosis, through three major transmembrane receptors on ER membrane, inositol requirement enzyme 1α, kinase-like kinase activating transcription factor 6. These modes of play occurrence development various diseases, such as neurodegenerative inflammation, metabolic liver injury. As largest organ, rich enzymes, carries out functions metabolism secretion, body's main site synthesis. Accordingly, a well-developed system present hepatocytes help perform its physiological functions. Current evidence suggests closely related stages injury, caused by may be key In addition, increasing modulating great potential for treating This article provided comprehensive overview relationship between four types death. Moreover, we discussed mechanism UPR injuries their therapeutic strategies.

Язык: Английский

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Overview of the Antioxidant and Anti-Inflammatory Activities of Selected Plant Compounds and Their Metal Ions Complexes

Molecules, Год журнала: 2021, Номер 26(16), С. 4886 - 4886

Опубликована: Авг. 12, 2021

Numerous plant compounds and their metal-ion complexes exert antioxidative, anti-inflammatory, anticancer, other beneficial effects. This review highlights the different bioactivities of flavonoids, chromones, coumarins metal-ions due to structural characteristics. In addition insight into most studied antioxidative properties these compounds, first part provides a comprehensive overview exogenous endogenous sources reactive oxygen nitrogen species, oxidative stress-mediated damages lipids proteins, on protective roles antioxidant defense systems, including plant-derived antioxidants. Additionally, covers anti-inflammatory antimicrobial activities which support its application in medicine, pharmacy, cosmetology.

Язык: Английский

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ER stress and UPR in Alzheimer’s disease: mechanisms, pathogenesis, treatments

Cell Death and Disease, Год журнала: 2022, Номер 13(8)

Опубликована: Авг. 15, 2022

Abstract Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes heavy burden on the healthcare system globally. Current therapeutics to interfere with underlying process in AD still under development. Although many efforts have centered toxic forms Aβ effectively tackle AD, considering unsatisfactory results so far it vital examine other targets therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers build-up unfolded or misfolded proteins within ER, thus, perturbing ER cellular homeostasis. Emerging evidence indicates that contributes onset development AD. A thorough elucidation machinery pathology may help open up new avenues management this condition relieve dementia symptoms. Herein, we aim at deciphering unique role pathogenesis, reviewing key findings, existing controversy an attempt summarize plausible interventions pathophysiology.

Язык: Английский

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Antioxidant Therapy in Cancer: Rationale and Progress

Antioxidants, Год журнала: 2022, Номер 11(6), С. 1128 - 1128

Опубликована: Июнь 8, 2022

Cancer is characterized by increased oxidative stress, an imbalance between reactive oxygen species (ROS) and antioxidants. Enhanced ROS accumulation, as a result of metabolic disturbances signaling aberrations, can promote carcinogenesis malignant progression inducing gene mutations activating pro-oncogenic signaling, providing possible rationale for targeting stress in cancer treatment. While numerous antioxidants have demonstrated therapeutic potential, their clinical efficacy remains unproven. Here, we review the for, recent advances in, pre-clinical research on antioxidant therapy cancer, including with nonenzymatic antioxidants, such NRF2 activators, vitamins, N-acetylcysteine GSH esters, or enzymatic NOX inhibitors SOD mimics. In addition, will offer insights into prospective options improving effectiveness therapy, which may expand its applications

Язык: Английский

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Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Апрель 20, 2023

Abstract Hypertension is a global public health issue and the leading cause of premature death in humans. Despite more than century research, hypertension remains difficult to cure due its complex mechanisms involving multiple interactive factors our limited understanding it. condition that named after clinical features. Vascular function factor affects blood pressure directly, it main strategy for clinically controlling BP regulate constriction/relaxation vessels. elasticity, caliber, reactivity are all characteristic indicators reflecting vascular function. Blood vessels composed three distinct layers, out which endothelial cells intima smooth muscle media performers The alterations signaling pathways these key molecular underlying dysfunction development. In this manuscript, we will comprehensively review involved regulation progression, including calcium pathway, NO-NOsGC-cGMP various remodeling some important upstream such as renin-angiotensin-aldosterone system, oxidative stress-related immunity/inflammation etc. Meanwhile, also summarize treatment methods targets discuss possibility being applied work.

Язык: Английский

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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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