The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review

Mostmans, Yora; Cutolo, Maurizio; Giddelo, Christina; Decuman, Saskia; Melsens, Karin; Declercq, Heidi; Vandecasteele, Els; Keyser, Filip De; Distler, Oliver; Gutermuth, Jan; Smith, Vanessa

doi:10.1016/j.autrev.2017.05.024

Cited by 157 publications

(129 citation statements)

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“…; Mostmans et al. ). Due to the unavailability of effective therapy, these vascular abnormalities often lead to severe morbidity and premature mortality (Leroy ; Herrick et al.…”

Section: Introductionmentioning

confidence: 98%

Rapid free thiol rebound is a physiological response following cold‐induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

et al. 2019

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Raynaud's phenomenon ( RP ) is often the first sign of systemic sclerosis ( SS c). Molecular mechanisms involved are incompletely understood, but reactive oxygen, nitrogen, and sulfur species are thought to play an important role in the pathogenesis of SS c. Free thiol groups play a protective role against oxidative stress and may represent an attractive therapeutic target. We aimed to investigate the effects of hypothermia‐induced vasoconstriction on the responsiveness of redox‐related markers. Thirty participants ( n = 10/group [ SS c, primary Raynaud's phenomenon ( PRP ), healthy controls ( HC )]) were included in this study. Fingertip photoelectric plethysmography was performed during a standardized cooling and recovery experiment. Venous blood was collected at four predetermined time points. Free thiols, NO ‐derived species (nitros(yl)ated species, nitrite, nitrate), sulfate and endothelin‐1 were measured. Lower baseline concentrations of free thiols were observed in PRP and SS c patients ( HC : 5.87 [5.41–5.99] μ mol/g; PRP : 5.17 [4.74–5.61]; SS c 5.28 [4.75–5.80], P = 0.04). Redox‐related markers remained unchanged during cooling. However, an unexpected increase in systemic free thiol concentrations was observed in all groups during the recovery phase. The response of this marker differed between groups, with a higher increase found in SS c patients ( HC Δ = 1.30 [1.48–1.17]; PRP Δ = 1.04 [1.06–1.03]; SS c Δ = 1.72 [1.13–1.49], P = 0.04). NO ‐derived species, sulfate and endothelin‐1 levels remained unchanged throughout the recovery phase. This exploratory study sheds light on the rapid responsiveness of systemic free thiol concentrations following reperfusion, which may reflect overall redox balance. The robust response to reperfusion in SS c patients suggests that reductive systems involved in this response are functionally intact in these patients.

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“…; Mostmans et al. ). Due to the unavailability of effective therapy, these vascular abnormalities often lead to severe morbidity and premature mortality (Leroy ; Herrick et al.…”

Section: Introductionmentioning

confidence: 98%

Rapid free thiol rebound is a physiological response following cold‐induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

et al. 2019

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“…Vasculopathy, which affects both small and large blood vessels, is characterized by endothelial dysfunction, perivascular infiltration of mononuclear cells, extracellular matrix remodeling in the vascular wall, and a loss of capillaries (capillary rarefaction) (Fleming et al, 2009; Mostmans et al, 2017). Raynaud’s phenomenon (RP) ( Figure 1 ), which manifests in the form of recurrent vasospastic attacks that cause episodic discoloration of the extremities in response to cold or emotional stress, is the hallmark of SSc and generally the first detectable sign of the disease (LeRoy and Medsger, 2001; Herrick, 2005; Gabrielli et al, 2009).…”

Section: Systemic Sclerosismentioning

confidence: 99%

“…The EC is believed to be a main target for pathological processes in SSc (Mostmans et al, 2017) and ROS have been implicated as having an important role in this process. In SSc, oxidative stress may cause the activation and damage of ECs (Grygiel-Górniak and Puszczewicz, 2014) leading to EC apoptosis and impairment of cell–cell adhesion (Sgonc et al, 1996).…”

Section: The Role Of Oxidative Stress In Ssc Vasculopathymentioning

confidence: 99%

“…The early phase of SSc is characterized by perivascular mononuclear cell infiltration (Mostmans et al, 2017) and the activation of the innate and adaptive immune system, which results in B-cell and T-cell activation (Amico et al, 2015). These cells secrete pro-inflammatory cytokines (including IL-1, IL-6, and IL-8) and chemokines that further stimulate ROS production (Murrell, 1993; Hua-Huy and Dinh-Xuan, 2015).…”

Section: The Role Of Oxidative Stress In Ssc Vasculopathymentioning

confidence: 99%

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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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“…Endothelial cell (EC) migration is important for a variety of physio logical and pathological conditions such as vasculogenesis, angiogenesis, wound healing, and atherogenesis (Lamalice, Le Boeuf, & Huot, 2007; Marcola & Rodrigues, 2015; Mostmans et al, 2017; Mudau, Genis, Lochner, & Strijdom, 2012; Tang & Conti, 2004). This complex multistep process involves protrusion of plasma membrane at the leading edges, formation of new adhesions at protrusion sites, and retraction of older adhesions at the rear and contraction.…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function

Shaaya

Harijith

et al. 2018

Current Topics in Membranes

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Sphingolipids, first described in the brain in 1884, are important structural components of biological membranes of all eukaryotic cells. In recent years, several lines of evidence support the critical role of sphingolipids such as sphingosine, sphingosine-1-phosphate (S1P), and ceramide as anti- or pro-inflammatory bioactive lipid mediators in a variety of human pathologies including pulmonary and vascular disorders. Among the sphingolipids, S1P is a naturally occurring agonist that exhibits potent barrier enhancing property in the endothelium by signaling via G protein-coupled S1P1 receptor. S1P, S1P analogs, and other barrier enhancing agents such as HGF, oxidized phospholipids, and statins also utilize the S1P/S1P1 signaling pathway to generate membrane protrusions or lamellipodia, which have been implicated in resealing of endothelial gaps and maintenance of barrier integrity. A better understanding of sphingolipids mediated regulation of lamellipodia formation and barrier enhancement of the endothelium will be critical for the development of sphingolipid-based therapies to alleviate pulmonary disorders such as sepsis-, radiation-, and mechanical ventilation-induced acute lung injury.

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The role of endothelial cells in the vasculopathy of systemic sclerosis: A systematic review

Cited by 157 publications

References 194 publications

Rapid free thiol rebound is a physiological response following cold‐induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

Rapid free thiol rebound is a physiological response following cold‐induced vasoconstriction in healthy humans, primary Raynaud and systemic sclerosis

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

Sphingolipids Signaling in Lamellipodia Formation and Enhancement of Endothelial Barrier Function

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