Redox regulation of endothelial cell fate

Song, Ping

doi:10.1007/s00018-014-1598-z

Cited by 38 publications

(27 citation statements)

References 261 publications

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“…Endothelial dysfunction is featured by increased endothelium apoptosis, impaired endothelial-dependent vasomotion, and dysregulated endothelial cell activation [88, 89]. Endothelial dysfunction accounts for a significant portion of all CVD [90].…”

Section: Role Of Dysregulated Kp In Cvdmentioning

confidence: 99%

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Song

Ramprasath

Wang

et al. 2017

Cell. Mol. Life Sci.

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172

134

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Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging. The first catabolic step in KP is primarily controlled by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Following this first step, the KP has two major branches, one branch is mediated by kynurenine 3-monooxygenase (KMO) and kynureninase (KYNU) and is responsible for the formation of 3-HK, 3-HAA, and quinolinic acid (QA); and another branch is controlled by kynurenine aminotransferase (KAT), which generates KA. Uncontrolled Trp catabolism has been demonstrated in distinct CVD, thus, understanding the underlying mechanisms by which regulates KP enzyme expression and activity is paramount. This review highlights the recent advances on the effect of KP enzyme expression and activity in different tissues on the pathological mechanisms of specific CVD, KP is an inflammatory sensor and modulator in the cardiovascular system, and KP catabolites act as the potential biomarkers for CVD initiation and progression. Moreover, the biochemical features of critical KP enzymes and principles of enzyme inhibitor development are briefly summarized, as well as the therapeutic potential of KP-enzyme inhibitors against CVD is briefly discussed.

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Section: Role Of Dysregulated Kp In Cvdmentioning

confidence: 99%

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Song

Ramprasath

Wang

et al. 2017

Cell. Mol. Life Sci.

Self Cite

172

134

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show abstract

“…Hyperglycemia in diabetes is believed to exacerbate atherosclerosis by promoting the release of reactive oxygen species (ROS) that damage sensitive cell components, such as DNA, cause premature cell death, and reduce nitric oxide (NO) availability, thus resulting in endothelial dysfunction (1). Several ROS-producing systems, including NADPH oxidases, uncoupled endothelial NO synthase (eNOS), and mitochondria, contribute to ROS generation (2). Increased mitochondrial ROS are critical for the initiation of endothelial dysfunction and the acceleration of atherosclerosis in diabetes (3).…”

Section: Introductionmentioning

confidence: 99%

Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission

et al. 2016

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Metformin is a widely used antidiabetic drug that exerts cardiovascular protective effects in patients with diabetes. How metformin protects against diabetes-related cardiovascular diseases remains poorly understood. Here, we show that metformin abated the progression of diabetes-accelerated atherosclerosis by inhibiting mitochondrial fission in endothelial cells. Metformin treatments markedly reduced mitochondrial fragmentation, mitigated mitochondrial-derived superoxide release, improved endothelial-dependent vasodilation, inhibited vascular inflammation, and suppressed atherosclerotic lesions in streptozotocin (STZ)-induced diabetic ApoE−/− mice. In high glucose–exposed endothelial cells, metformin treatment and adenoviral overexpression of constitutively active AMPK downregulated mitochondrial superoxide, lowered levels of dynamin-related protein (Drp1) and its translocation into mitochondria, and prevented mitochondrial fragmentation. In contrast, AMPK-α2 deficiency abolished the effects of metformin on Drp1 expression, oxidative stress, and atherosclerosis in diabetic ApoE−/−/AMPK-α2−/− mice, indicating that metformin exerts an antiatherosclerotic action in vivo via the AMPK-mediated blockage of Drp1-mediated mitochondrial fission. Consistently, mitochondrial division inhibitor 1, a potent and selective Drp1 inhibitor, reduced mitochondrial fragmentation, attenuated oxidative stress, ameliorated endothelial dysfunction, inhibited inflammation, and suppressed atherosclerosis in diabetic mice. These findings show that metformin attenuated the development of atherosclerosis by reducing Drp1-mediated mitochondrial fission in an AMPK-dependent manner. Suppression of mitochondrial fission may be a therapeutic approach for treating macrovascular complications in patients with diabetes.

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“…Aberrant ROS production causes oxidative modification on proteins and/or nucleic acids (such as DNA). Heightened oxidative stress is widely considered as common pathways for the initiation and progression of CVD, including atherosclerosis, hypertension, and heart failure [1]. Therefore, alterations to physiologic ROS levels represents a common and potent mediator of pathogenic risk factors associated with cardiovascular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Measurement of Reactive Oxygen Species (ROS) and Mitochondrial ROS in AMPK Knockout Mice Blood Vessels

Wang

Zou

2018

Methods in Molecular Biology

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Reactive oxygen species (ROS) are a group of unstable and highly reactive molecules or free radicals typically generated as by-products of cellular processes involving molecular oxygen. In vascular cells, the excessive ROS generation results in the initiation and progression of cardiovascular diseases (CVD). Therefore, a dynamic, robust, and accurate ROS detection method in the blood vessels is essential for pathophysiological research studies of the cardiovascular system.In this chapter, we describe a fluorescence dye-based detection method for assaying superoxide and mitochondrial superoxide in mouse aorta using dihydroethidium (DHE) and MitoSOX. The protocol includes preparation of frozen aortic tissue sections, monitoring DHE oxidation-derived fluorescence by fluorescence microscopy, and high-performance liquid chromatograph-based analysis of MitoSOX and its oxidation products. For studying the role of AMP-activated protein kinase (AMPK) in the redox regulation, we employed AMPKα2 knockout mice and observed increased superoxide and mitochondrial superoxide levels in the aorta of AMPK knockout mice relative to the wild-type group. This novel ROS detection method will be valuable for investigating the roles of cellular and/or mitochondrial ROS in the pathogenesis of CVDs.

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Redox regulation of endothelial cell fate

Cited by 38 publications

References 261 publications

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases

Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission

Measurement of Reactive Oxygen Species (ROS) and Mitochondrial ROS in AMPK Knockout Mice Blood Vessels

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