Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma

Romero, Luz; Zhang, Dan-Ning; Cooke, John P.; Ho, Hoai-Ky V; Avalos, Esperanza; Herrera, Rafael Vega; Herron, G. Scott

doi:10.1177/1358836x0000500304

Cited by 67 publications

(7 citation statements)

References 71 publications

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“…It was previously suggested that a decreased release of NO, which may lead to impaired endothelial-dependent vasodilatation, might play an important role in the pathogenesis of the SSc-related vasculopathy. In support, several studies reported a decreased level of NO release [29,30]. Subsequently, this may promote the development of vasculopathy by inducing recurrent RP attacks, increasing vascular wall thickness, and by enhancing the platelet aggregation.…”

Section: Role Of Nitric Oxide and Carbon Monoxide In Systemic Sclementioning

confidence: 75%

Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

Abdulle

Goor

Mulder

2018

IJMS

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Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.

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Section: Role Of Nitric Oxide and Carbon Monoxide In Systemic Sclementioning

confidence: 75%

Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

Abdulle

Goor

Mulder

2018

IJMS

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“…Notably, senescent endothelial cells also undergo endothelial-to-mesenchymal transition (Endo-MT), a process that contributes to organ fibrosis [10 ▪ ]. Recent studies reveal that these changes phenocopy the hallmarks of SSc endothelial cells [11–13], suggesting that cellular senescence is associated with, and might play a role in, endothelial dysfunction in SSc.…”

Section: Implications Of Cellular Senescence For Systemic Sclerosis P...mentioning

confidence: 99%

“…Recent studies reveal that these changes phenocopy the hallmarks of SSc endothelial cells [11][12][13], suggesting that cellular senescence is associated with, and might play a role in, endothelial dysfunction in SSc.…”

Section: Vasculopathy-endothelial Cellsmentioning

confidence: 99%

Role of cellular senescence in the pathogenesis of systemic sclerosis

Tsou

Shi

Varga

2022

Current Opinion in Rheumatology

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Purpose of reviewSystemic sclerosis (SSc) is a chronic rheumatic disease that is characterized by immune activation, vasculopathy and fibrosis of the skin and internal organs. It has been proposed that premature onset of ageing pathways and associated senescent changes in cells contribute to the clinical and pathological features of SSc. The aim of this review is to critically review recent insights into the involvement of cellular senescence in SSc.Recent findingsCellular senescence plays a critical role in SSc pathogenesis, particularly involving endothelial cells and fibroblasts. Immunosenescence could also contribute to SSc pathogenesis by direct alteration of cellular functions or indirect promotion of defective immune surveillance. Molecular studies have shed some light on how cellular senescence contributes to fibrosis. Recent and planned proof-of-concept trials using senotherapeutics showed promising results in fibrotic diseases, including SSc.SummaryThere is increasing evidence implicating cellular senescence in SSc. The mechanisms underlying premature cellular senescence in SSc, and its potential role in pathogenesis, merit further investigation. Emerging drugs targeting senescence-related pathways might be potential therapeutic options for SSc.

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“…This impairment ultimately increases vascular endothelial permeability, subsequently leading to alterations in EC signal transduction (Fleischmajer and Perlish, 1980). When damaged, vascular ECs produce increased levels of vasoconstrictive mediators (e.g., endothelin-1 [ET-1]) and show an impaired release of NO and prostacyclin (Freedman et al, 1999; Romero et al, 2000; Matucci Cerinic and Kahaleh, 2002). This imbalance in mediators, in addition to several other oxidative and non-oxidative pathways (e.g., the adrenergic mechanism), results in altered vascular tone in favor of vasoconstriction.…”

Section: The Role Of Oxidative Stress In Ssc Vasculopathymentioning

confidence: 99%

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

et al. 2018

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Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as ‘Raynaud’s phenomenon,’ which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

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Differential expression of nitric oxide by dermal microvascular endothelial cells from patients with scleroderma

Cited by 67 publications

References 71 publications

Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

Role of cellular senescence in the pathogenesis of systemic sclerosis

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

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