Systemic Sclerosis: A Key Model of Endothelial Dysfunction.

Area of Science:

• Rheumatology
• Vascular Biology
• Immunology

Background:

• Systemic sclerosis (SSc) is a complex autoimmune disease featuring vascular damage, immune system dysregulation, and fibrosis.
• Endothelial dysfunction is increasingly recognized as a central mechanism in SSc pathogenesis and vascular injury.

Purpose of the Study:

• To review the role of persistent endothelial dysfunction in systemic sclerosis (SSc).
• To explore how endothelial dysfunction contributes to SSc pathogenesis, fibrotic remodeling, and clinical manifestations.
• To identify potential therapeutic targets based on endothelial dysfunction in SSc.

Main Methods:

• Narrative review of existing literature on systemic sclerosis and endothelial function.
• Analysis of mechanisms including oxidative stress, autoimmunity, impaired vascular repair, angiogenesis, vasculogenesis, endothelial progenitor cell function, and endothelial-to-mesenchymal transition.
• Correlation of endothelial dysfunction with hallmark SSc clinical features.

Main Results:

• Endothelial dysfunction, stemming from oxidative stress and autoimmunity, triggers and sustains organ fibrosis in SSc.
• Impaired angiogenesis, vasculogenesis, reduced endothelial progenitor cell function, and endothelial-to-mesenchymal transition disrupt vascular homeostasis and activate myofibroblasts.
• These processes explain key SSc manifestations like Raynaud's phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis.

Conclusions:

• Systemic sclerosis can be viewed as a systemic endothelial dysfunction disorder.
• Reframing SSc through the lens of endothelial dysfunction may alter understanding of its pathophysiology.
• This perspective may lead to modified therapeutic strategies and the discovery of novel treatment targets for SSc.