Mitochondrial monoamine oxidase‐A‐mediated hydrogen peroxide generation enhances 5‐hydroxytryptamine‐induced contraction of rat basilar artery

Poon, Chi‐Ming; Seto, Sai Wang; Au, Alice Lai Shan; Zhang, Qian; Li, Rachel Wai Sum; Lee, Wayne; Leung, George Pak-Heng; Kong, Siu Kai; Yeung, John H.K.; Ngai, Sai Ming; Ho, Ho Pui; Lee, Simon Ming‐Yuen; Chan, Shun‐Wan; Kwan, Yiu Wa

doi:10.1111/j.1476-5381.2010.00941.x

Cited by 21 publications

(20 citation statements)

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“…Previous studies have demonstrated that the increased vascular formation of ROS after supplementation with serotonin was in part MAO mediated. 33 It was, however, not studied whether this effect occurs without supplementation of substrate, that is, whether endogenous vascular catecholamines are sufficient to fuel MAOs. Adventitial nerves produce norepinephrine, and platelets positioned at the endothelial surface could serve as a source of serotonin.…”

Section: Discussionmentioning

confidence: 99%

Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta

Sturza

Leisegang²,

Bábelová³

et al. 2013

Hypertension

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Abstract-Monoamine oxidases (MAOs) generate H 2 O 2 as a by-product of their catalytic cycle. Whether MAOs are mediators of endothelial dysfunction is unknown and was determined here in the angiotensin II and lipopolysaccharidemodels of vascular dysfunction in mice. Quantitative real-time polymerase chain reaction revealed that mouse aortas contain enzymes involved in catecholamine generation and MAO-A and MAO-B mRNA. MAO-A and -B proteins could be detected by Western blot not only in mouse aortas but also in human umbilical vein endothelial cells. Ex vivo incubation of mouse aorta with recombinant MAO-A increased H 2 O 2 formation and induced endothelial dysfunction that was attenuated by polyethylene glycol-catalase and MAO inhibitors. In vivo lipopolysaccharide (8 mg/kg IP overnight) or angiotensin II (1 mg/kg per day, 2 weeks, minipump) treatment induced vascular MAO-A and -B expressions and resulted in attenuated endothelium-dependent relaxation of the aorta in response to acetylcholine. MAO inhibitors reduced the lipopolysaccharide-and angiotensin II-induced aortic reactive oxygen species formation by 50% (ferrous oxidation xylenol orange assay) and partially normalized endothelium-dependent relaxation. MAO-A and MAO-B inhibitors had an additive effect; combined application completely restored endothelium-dependent relaxation. To determine how MAO-dependent H 2 O 2 formation induces endothelial dysfunction, cyclic GMP was measured. Histamine stimulation of human umbilical vein endothelial cells to activate endothelial NO synthase resulted in an increase in cyclic GMP, which was almost abrogated by MAO-A exposure. MAO inhibition prevented this effect, suggesting that MAO-induced H 2 O 2 formation is sufficient to attenuate endothelial NO release. Sturza et al MAOs in Endothelial Dysfunction 141MAO-A-mediated H 2 O 2 production has been shown to be relevant for ischemia-reperfusion injury of the kidney 11 and the heart. Moreover, MAO-A is thought to be involved in myocyte hypertrophy ex vivo 12,13 and also in maladaptive myocardial hypertrophy and transition to heart failure in vivo.14 The unfavorable effects of MAO activation are antagonized by a couple of relatively selective MAO inhibitors, which are either irreversible, such as clorgyline for MAO-A and selegiline for MAO-B, or reversible, such as moclobemide for MAO-A and lazabemide for MAO-B, respectively.8 Systemic MAO inhibition leads to the accumulation of catecholamines with subsequent increase in sympathetic activity and hypertension. 15 This aspect limits the use of MAO inhibitors in a vascular scenario, and therefore, MAO inhibitors have not been considered an approach to improve vascular function.Another prototypic hypertensive agent is angiotensin II (Ang II). Interestingly, potential interactions of Ang II and MAOs have been reported in the central nervous system. In coculture systems of hypothalamic and brain stem neurons, Ang II stimulated MAO activity, but the underlying mechanism was not studied. 16 More recently, it was reported that in...

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Section: Discussionmentioning

confidence: 99%

Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta

Sturza

Leisegang²,

Bábelová³

et al. 2013

Hypertension

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“…Moreover, the monoamine oxidase (MAO) family of enzymes-which is found in the outer mitochondrial membrane-generates hydrogen peroxide (H 2 O 2 ) during catabolism of catecholamines and has been implicated in maladaptive cellular hypertrophy and apoptosis (35). MAO-Ainduced ROS are involved in serotonin-induced vasoconstriction in vascular smooth muscle cells (36). Although endothelial cells are known to express MAO, its importance for endothelial function is poorly understood (37).…”

Section: Mitochondrial Rosmentioning

confidence: 99%

Epigenetic Control of Mitochondrial Function in the Vasculature

Mohammed

Ambrosini

Lüscher

et al. 2020

Front. Cardiovasc. Med.

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The molecular signatures of epigenetic regulation and chromatin architecture are emerging as pivotal regulators of mitochondrial function. Recent studies unveiled a complex intersection among environmental factors, epigenetic signals, and mitochondrial metabolism, ultimately leading to alterations of vascular phenotype and increased cardiovascular risk. Changing environmental conditions over the lifetime induce covalent and post-translational chemical modification of the chromatin template which sensitize the genome to establish new transcriptional programs and, hence, diverse functional states. On the other hand, metabolic alterations occurring in mitochondria affect the availability of substrates for chromatin-modifying enzymes, thus leading to maladaptive epigenetic signatures altering chromatin accessibility and gene transcription. Indeed, several components of the epigenetic machinery require intermediates of cellular metabolism (ATP, AcCoA, NADH, α-ketoglutarate) for enzymatic function. In the present review, we describe the emerging role of epigenetic modifications as fine tuners of gene transcription in mitochondrial dysfunction and vascular disease. Specifically, the following aspects are described in detail: (i) mitochondria and vascular function, (ii) mitochondrial ROS, (iii) epigenetic regulation of mitochondrial function; (iv) the role of mitochondrial metabolites as key effectors for chromatin-modifying enzymes; (v) epigenetic therapies. Understanding epigenetic routes may pave the way for new approaches to develop personalized therapies to prevent mitochondrial insufficiency and its complications.

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“…64 Hydrogen peroxide produced by MAO-A in vascular smooth muscle cells contributes to serotonin-induced vasoconstriction. 65 Although endothelial cells are known to express MAO, 66 its importance for endothelial function is poorly understood.…”

Section: Mitochondrial Ros In Endothelial Cellsmentioning

confidence: 99%

Mitochondria and Endothelial Function

Kluge

Fetterman

Vita

2013

Circulation Research

405

365

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In contrast to their role in other cell types with higher energy demands, mitochondria in endothelial cells primarily function in signaling cellular responses to environmental cues. This article provides an overview of key aspects of mitochondrial biology in endothelial cells, including subcellular location, biogenesis, dynamics, autophagy, ROS production and signaling, calcium homeostasis, regulated cell death, and heme biosynthesis. In each section, we introduce key concepts and then review studies showing the importance of that mechanism to endothelial control of vasomotor tone, angiogenesis, and inflammatory activation. We particularly highlight the small number of clinical and translational studies that have investigated each mechanism in human subjects. Finally, we review interventions that target different aspects of mitochondrial function and their effects on endothelial function. The ultimate goal of such research is the identification of new approaches for therapy. The reviewed studies make it clear that mitochondria are important in endothelial physiology and pathophysiology. A great deal of work will be needed, however, before mitochondria-directed therapies are available for the prevention and treatment of cardiovascular disease.

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Mitochondrial monoamine oxidase‐A‐mediated hydrogen peroxide generation enhances 5‐hydroxytryptamine‐induced contraction of rat basilar artery

Cited by 21 publications

References 59 publications

Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta

Monoamine Oxidases Are Mediators of Endothelial Dysfunction in the Mouse Aorta

Epigenetic Control of Mitochondrial Function in the Vasculature

Mitochondria and Endothelial Function

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