Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1

Ali, Ziad A.; Perez, Vinicio de Jesus; Yuan, Ke; Orcholski, Mark; Pan, Stephen; Qi, Wei; Chopra, Gaurav; Adams, Christopher M.; Kojima, Yoshiyuki; Leeper, Nicholas J.; Qu, Xiumei; Zaleta-Rivera, Kathia; Kato, Koichi; Yamada, Yoshiji; Oguri, Mitsutoshi; Kuchinsky, Allan; Hazen, Stanley L.; Jukema, J Wouter; Ganesh, Santhi K.; Nabel, Elizabeth G.; Channon, Keith M.; Leon, Martin B.; Charest, Alain; Quertermous, Thomas; Ashley, Euan A.

doi:10.1172/jci77484

Cited by 40 publications

(25 citation statements)

References 56 publications

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“…Network analysis of gene expression in human carotid neointima showed that the most significantly downregulated network was the one with GPX1 in its hub. 81 Furthermore, Apoe −/− mice with deleted Gpx1 were characterized with increased atherosclerotic plaque, which contained more SMCs but not macrophages. However, increased macrophage infiltration in Gpx1 −/− Apoe −/− was previously reported by Torzewski et al 41 Furthermore, balloon angioplasty and stenting in Gpx1 +/+ Apoe −/− mice decreased Gpx1 expression.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Reactive Oxygen Species Generation and Atherosclerosis

Nowak

Deng

Ruan

et al. 2017

ATVB

136

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Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Reactive Oxygen Species Generation and Atherosclerosis

Nowak

Deng

Ruan

et al. 2017

ATVB

136

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“…It is highly likely that reductive stress via s-glutathionylation of important proteins contributes to vascular remodeling associated with these risk factors. In this issue of the JCI, Ali et al (10) identify GPX1 as the network hub gene capable of mediating both reductive and oxidative stress in VSMCs. Perturbations in reductive stress may turn out to be as important, if not more important, than oxidative stress, as demonstrated in in-stent stenosis, with clinical implications that may extend beyond BAS.…”

Section: Discussionmentioning

confidence: 99%

“…Using a networks approach to compare coronary vascular gene expression between de novo atherosclerosis and in-stent stenosis patients, Ali et al (10) identified GPX1 as the network hub gene involved in pathological remodeling following stenting. Evaluation of SNPs and confirmation with GWAS revealed that mutations within GPX1 and the orphan protooncogene receptor tyrosine kinase ROS1 are tightly associated with in-stent stenosis.…”

Section: Gpx1: At the Center Of Stentinduced Pathologic Remodelingmentioning

confidence: 99%

“…While previous studies on GPX1 in vascular injury have focused on its role in atherosclerosis, particularly the involvement of GPX1 in immune cells (9), the role of GPX1 in VSMCs, the drivers of stenosis, has not been characterized. In this issue of the JCI, Ali et al (10) demonstrate that vascular injury-induced loss of GPX1 alters oxidoreductive stress in VSMCs and promotes in-stent stenosis. This study opens up new frontiers for in-stent stenosis research and therapy and also highlights the need to look further afield at reductive stress when dealing with imbalances in redox events.…”

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confidence: 99%

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Limiting reductive stress for treating in-stent stenosis: the heart of the matter?

de Haan

2014

J. Clin. Invest.

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C o m m e n t a r y 5 0 9 2 jci.org Volume 124 Number 12 December 2014Limiting reductive stress for treating in-stent stenosis: the heart of the matter? Judy B. de HaanBaker IDI Heart and Diabetes Institute, Diabetic Complications Division, Oxidative Stress Laboratory, Melbourne, Victoria, Australia. Vascular injury and drivers of stenosisBalloon angioplasty and stenting (BAS) remains the preferred method of treatment for flow-limiting atherosclerosis, far outnumbering coronary artery bypass grafting (1). Unfortunately, stent-mediated intimal hyperplasia, a consequence of vascular smooth muscle cell (VSMC) proliferation, remains a cause of restenosis after BAS and often presents with acute coronary syndrome. Reendothelialization of the damaged vessel has been proposed to reduce intimal hyperplasia; however, current treatment options, such as drugeluting stents, aimed at limiting VSMC proliferation may also inhibit reendothelialization. Reduced reendothelialization leads to an increased risk of thrombosis within the stented vessel, often resulting in devastating clinical consequences (2). Thus, there is a clinical need for improvements in the treatment of flow-limiting atherosclerosis. Recent advances have been made in preclinical models, including the use of mesenchymal stem cells (3) and miRNA-based strategies (4), to assist with reendothelialization. The potential for these new approaches to lead to clinical breakthroughs will likely be expedited once the mechanisms behind BAS-driven hyperplasia are better understood. Over the past decade, there has been a groundswell of clinical and preclinical evidence that indicates the antioxidant enzyme glutathione peroxidase-1 (GPX1) is involved in the atherogenic process. Clinically, low levels of GPX1 have been associated with an increased risk of cardiovascular events in patients with coronary artery disease, independent of traditional risk factors (5), and GPX1 activity has also been shown to be reduced in excised human plaques (6). Preclinically, plaque analysis in atherosclerosis-prone mice revealed that a lack of GPX1 accelerates plaque formation under both hyperlipidemic (7) and diabetic (8) conditions. While previous studies on GPX1 in vascular injury have focused on its role in atherosclerosis, particularly the involvement of GPX1 in immune cells (9), the role of GPX1 in VSMCs, the drivers of stenosis, has not been characterized. In this issue of the JCI, Ali et al. (10) demonstrate that vascular injury-induced loss of GPX1 alters oxidoreductive stress in VSMCs and promotes in-stent stenosis. This study opens up new frontiers for in-stent stenosis research and therapy and also highlights the need to look further afield at reductive stress when dealing with imbalances in redox events. GPX1 is known to perform important functions in limiting reactive oxygen species-mediated lipid, protein, and DNA damage (11); therefore, the oxidative stress that results from a decline in GPX1 levels has been touted as the mediator of injury. The current report from Ali and coll...

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“…This seminal study was amongst the first to demonstrate a distinct role for reductive stress in human cardiac disease (12). More recently, this notion has been extended to vascular disease in humans where loss of function of glutathione peroxidase-1 (GPX1) was found to induce both oxidative and reductive stress, with reductive stress driving Sglutathionylation of ROS1 tyrosine phosphatase SHP-2 and processes leading to vascular remodelling (13). These finding, together with those highlighted in the current issue (4), suggest that it is timely to rethink the current dogma that oxidative stress is the major redox contributor to pathological processes underlying cardiovascular disease.…”

mentioning

confidence: 99%