Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis

López-Armada, M.J.; Fernández-Rodríguez, Jennifer Adriana; Blanco, Francisco J.

doi:10.3390/antiox11061151

Cited by 25 publications

(12 citation statements)

References 303 publications

(401 reference statements)

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“…These agents suppress mitochondrial-generated OS. It also reinforces the need to study natural antioxidant agents known to reduce OS due to mitochondria, such as omega-3 and resveratrol ( 154 ). Clinically, it is reasonable to believe that management of autoimmune diseases focused on reducing OS will retard the pathogenesis of atherosclerosis and decrease the chronic association between lipids and inflammation.…”

Section: Traditional and Emerging CV Risksmentioning

confidence: 59%

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

Bale

Doneen

Leimgruber

et al. 2022

Front. Cardiovasc. Med.

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The formation of an atheroma begins when lipoproteins become trapped in the intima. Entrapped lipoproteins become oxidized and activate the innate immune system. This immunity represents the primary association between lipids and inflammation. When the trapping continues, the link between lipids and inflammation becomes chronic and detrimental, resulting in atherosclerosis. When entrapment ceases, the association between lipids and inflammation is temporary and healthy, and the atherogenic process halts. Therefore, the link between lipids and inflammation depends upon lipoprotein retention in the intima. The entrapment is due to electrostatic forces uniting apolipoprotein B to polysaccharide chains on intimal proteoglycans. The genetic transformation of contractile smooth muscle cells in the media into migratory secretory smooth muscle cells produces the intimal proteoglycans. The protein, platelet-derived growth factor produced by activated platelets, is the primary stimulus for this genetic change. Oxidative stress is the main stimulus to activate platelets. Therefore, minimizing oxidative stress would significantly reduce the retention of lipoproteins. Less entrapment decreases the association between lipids and inflammation. More importantly, it would halt atherogenesis. This review will analyze oxidative stress as the critical link between lipids, inflammation, and the pathogenesis of atherosclerosis. Through this perspective, we will discuss stopping oxidative stress to disrupt a harmful association between lipids and inflammation. Numerous therapeutic options will be discussed to mitigate oxidative stress. This paper will add a new meaning to the Morse code distress signal SOS-stopping oxidative stress.

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Section: Traditional and Emerging CV Risksmentioning

confidence: 59%

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

Bale

Doneen

Leimgruber

et al. 2022

Front. Cardiovasc. Med.

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“…Increasing evidence has demonstrated the role of mitochondrial alterations in RA mainly due to the interplay between metabolism and innate immunity and the modulation of the inflammatory response of FLS. Mitochondrial dysfunction derived from several danger signals could activate tricarboxylic acid (TCA) disruption, creating a vicious cycle of oxidative-mitochondrial stress [ 57 ]. Our microarray analyses showed that several mitochondrial metabolism genes, including Ak3, Idh3a, Idh3B, Idh3g, Asl, and Acyl, were deregulated by the CFA, suggesting the alteration of TCA.…”

Section: Discussionmentioning

confidence: 99%

Complete Freund’s Adjuvant Induces a Fibroblast-like Synoviocytes (FLS) Metabolic and Migratory Phenotype in Resident Fibroblasts of the Inoculated Footpad at the Earliest Stage of Adjuvant-Induced Arthritis

González-Chávez

Chaparro-Barrera

Alvarado-Jáquez

et al. 2023

Cells

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The fibroblast-like synoviocytes (FLS) have a crucial role in the pathogenesis of Rheumatoid Arthritis (RA); however, its precise mechanisms remain partially unknown. The involvement of the fibroblast in activating adjuvant-induced arthritis (AA) has not been previously reported. The objective was to describe the participation of footpads’ fibroblasts in the critical initial process that drives the AA onset. Wistar rats were injected with Complete Freund’s Adjuvant (CFA) or saline solution in the hind paws’ footpads and euthanized at 24 or 48 h for genetic and histological analyses. Microarrays revealed the differentially expressed genes between the groups. The CFA dysregulated RA-linked biological processes at both times. Genes of MAPK, Jak-STAT, HIF, PI3K-Akt, TLR, TNF, and NF-κB signaling pathways were altered 24 h before the arrival of immune cells (CD4, CD8, and CD68). Key markers TNF-α, IL-1β, IL-6, NFκB, MEK-1, JAK3, Enolase, and VEGF were immunodetected in fibroblast in CFA-injected footpads at 24 h but not in the control group. Moreover, fibroblasts in the CFA inoculation site overexpressed cadherin-11, which is linked to the migration and invasion ability of RA-FLS. Our study shows that CFA induced a pathological phenotype in the fibroblast of the inoculation site at very early AA stages from 24 h, suggesting a prominent role in arthritis activation processes.

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“…This favors the balance toward the process of bone resorption, causing bone destruction, while ROS affect the release of MMPs and activity of chondrocytes, exacerbating cartilage damage ( 39 – 41 ). Therefore, both ROS and mitochondrial damage are involved in the development of RA ( 42 , 43 ). In a randomized controlled trial, Yoga was shown to enhance mitochondrial quality, reduce oxidative stress marker production, and improve the Disease Activity Score-Erythrocyte Sedimentation Rate and Health Assessment Questionnaire-Disability Index scores in patients with RA, which may be a beneficial adjunct to training for RA ( 44 ).…”

Section: Ros and Mitochondrial Damage In Ramentioning

confidence: 99%

Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

et al. 2023

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Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation, pannus formation, and bone and cartilage damage. It has a high disability rate. The hypoxic microenvironment of RA joints can cause reactive oxygen species (ROS) accumulation and mitochondrial damage, which not only affect the metabolic processes of immune cells and pathological changes in fibroblastic synovial cells but also upregulate the expression of several inflammatory pathways, ultimately promoting inflammation. Additionally, ROS and mitochondrial damage are involved in angiogenesis and bone destruction, thereby accelerating RA progression. In this review, we highlighted the effects of ROS accumulation and mitochondrial damage on inflammatory response, angiogenesis, bone and cartilage damage in RA. Additionally, we summarized therapies that target ROS or mitochondria to relieve RA symptoms and discuss the gaps in research and existing controversies, hoping to provide new ideas for research in this area and insights for targeted drug development in RA.

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Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis

Cited by 25 publications

References 303 publications

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

The critical issue linking lipids and inflammation: Clinical utility of stopping oxidative stress

Complete Freund’s Adjuvant Induces a Fibroblast-like Synoviocytes (FLS) Metabolic and Migratory Phenotype in Resident Fibroblasts of the Inoculated Footpad at the Earliest Stage of Adjuvant-Induced Arthritis

Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

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