Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid

Tian, Rong; Ding, Yun; Peng, Yiyuan; Lu, Naihao

doi:10.1016/j.bbrc.2017.01.132

Cited by 46 publications

(74 citation statements)

References 25 publications

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“…As NADPH oxidase-derived ROS and vascular-bound MPO are increased in diabetic vessels, MPO/NADPH oxidase/H2O2/HOCl could constitute a main path in diabetic vascular damages. According Tian et al blocking the MPO-NADPH oxidase-HOCl pathway could be a novel therapeutic strategy for the prevention and the recovery of vascular diseases [ 39 ].…”

Section: Methodsmentioning

confidence: 99%

Chlorinative stress in age-related diseases: a literature review

et al. 2017

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Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.

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Section: Methodsmentioning

confidence: 99%

Chlorinative stress in age-related diseases: a literature review

et al. 2017

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“…Thus, an impaired endonuclease activity is typical for SLE patients with LN or SLE patients with increased SLEDAI and other non-renal clinical complications ( 40 ). Undegraded NETs can ultimately deposit in the glomerular capillaries, where they may exacerbate renal inflammation by activation of complement via bound Ig, or by their cytotoxic histones and/or cytotoxic enzymes (e.g., MPO, NE) ( 41 – 43 ). This is in line with findings of circulating NET fragments and skin or renal NET depositions in lupus-prone mice and SLE patients ( 44 ), suggesting a pathogenic involvement of NETs in SLE.…”

Section: Discussionmentioning

confidence: 99%

Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis

et al. 2017

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ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Lupus nephritis (LN) is the major cause of morbidity and mortality in patients with SLE. Central to the pathogenesis of SLE is the accumulation of cellular waste, especially apoptotic microparticles (MPs), which stimulates diverse immune reactions including the formation of neutrophil extracellular traps (NETs). In this study, we investigated the content of MPs from SLE patients with and without (active) LN, their capacity to stimulate NET release, and assessed the molecular mechanisms underlying MP-induced NETosis.MethodsMPs from SLE patients with biopsy-proven active LN, remissive LN, without LN, and healthy controls were characterized by flow cytometry. Isolated neutrophils were exposed to MPs derived from either patient plasma or apoptotic human umbilical vein endothelial cells, and NET release was quantified by immunofluorescence imaging, spectrofluorometry or an in-house developed NET ELISA.ResultsMPs from SLE patients with active LN contain higher levels of acetylated chromatin compared to MPs from those with remissive LN, without LN, or healthy controls. MPs enriched in hyperacetylated chromatin are more potent in inducing NETosis when compared to MPs containing moderate acetylated chromatin. The release of NETs in response to MPs occurs rapidly in a concentration-dependent manner and proceeds independent from the formation of reactive oxygen species (ROS).ConclusionOur data suggest that MPs containing acetylated chromatin drive ROS-independent NET release in SLE patients with active LN, which may lead to the glomerular deposition of NETs and subsequent NET-driven LN.

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“…Hydrogen peroxide can also be metabolized by neutrophilic myeloperoxidase (MPO) to form hypochlorous acid and other oxidizing species. MPO can also act as an NO oxidase, thereby reducing the bioactivity of NO and increasing oxidative stress, thereby contributing to EDD dysfunction (Baldus, Heitzer, Eiserich, Lau, Mollnau, Ortak et al, 2004; Tian, Ding, Peng & Lu, 2017). …”

Section: Ang Ii-dependent Nad(p)h Oxidase-mediated Production Of Reamentioning

confidence: 99%

Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction

Korthuis

2018

Advances in Pharmacology

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Ischemia/reperfusion (I/R) induces leukocyte/endothelial cell adhesive interactions (LECA) in postcapillary venules and impaired endothelium-dependent, NO-mediated dilatory responses (EDD) in upstream arterioles. A large body of evidence has implicated reactive oxygen species (ROS), adherent leukocytes, and proteases in postischemic EDD dysfunction in conduit arteries. However, arterioles represent the major site for the regulation of vascular resistance, but have received less attention with regard to the mechanisms underlying their reduced responsiveness to EDD stimuli in I/R. Even though leukocytes do not roll along, adhere to, or emigrate across arteriolar endothelium in postischemic intestine, recent work indicates that I/R-induced venular LECA is causally linked to EDD in arterioles. An emerging body of evidence supports the view that I/R-induced EDD in arterioles occurs by a mechanism that is triggered by LECA in postcapillary venules and involves the formation of signals in the interstitium elicited by the proteolytic activity of emigrated leukocytes. This activity releases matricryptins from or exposes matricryptic sites in the extracellular matrix (ECM) that interact with the integrin αvβ3 to induce mast cell chymase-dependent formation of angiotensin II (Ang II). Subsequent activation of NAD(P)H oxidase by Ang II leads to the formation of oxidants which inactivate NO, resulting in arteriolar EDD dysfunction. ROS generation also promotes eNOS uncoupling in the vascular wall, exacerbating impaired EDD responses. This work establishes new links between LECA in postcapillary venules, signals generated in the interstitium by emigrated leukocytes, mast cell degranulation, and impaired EDD in upstream arterioles. Given the importance of the endothelium in regulating vascular tone, these fundamentally important findings have enormous implications for our understanding of blood flow dysregulation in conditions characterized by I/R.

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Myeloperoxidase amplified high glucose-induced endothelial dysfunction in vasculature: Role of NADPH oxidase and hypochlorous acid

Cited by 46 publications

References 25 publications

Chlorinative stress in age-related diseases: a literature review

Chlorinative stress in age-related diseases: a literature review

Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis

Mechanisms of I/R-Induced Endothelium-Dependent Vasodilator Dysfunction

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