Decoding vascular dysfunction in systemic sclerosis: from endothelial damage to clinical implications

Area of Science:

• Rheumatology
• Vascular Biology
• Immunology

Background:

• Vascular dysfunction is a critical component of systemic sclerosis (SSc), impacting patient morbidity and mortality.
• Understanding the mechanisms of SSc vasculopathy is crucial for developing effective treatments.

Purpose of the Study:

• To review the current understanding of vascular dysfunction in SSc.
• To explore the role of endothelial cell (EC) injury, senescence, and transition in SSc.
• To discuss emerging diagnostic tools and therapeutic strategies for SSc vasculopathy.

Main Methods:

• Literature review of recent advances in SSc vascular research.
• Analysis of molecular profiling techniques like single-cell and spatial omics.
• Examination of clinical manifestations and diagnostic approaches.

Main Results:

• Endothelial cell (EC) injury, senescence, and endothelial-to-mesenchymal transition are key to SSc vasculopathy.
• Omics studies reveal distinct EC subtypes and dysregulated pathways (e.g., interferon signaling).
• Clinical complications include Raynaud's phenomenon, digital ulcers, pulmonary arterial hypertension, and renal crisis; nailfold capillaroscopy aids early detection.

Conclusions:

• Vascular dysfunction is a hallmark and driver of SSc progression.
• Molecular profiling and imaging enhance understanding and identify therapeutic targets.
• Early diagnosis, biomarker-guided care, and multidisciplinary management are vital for improved SSc outcomes.