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Updated: Apr 24, 2026
Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test
Published on: April 27, 2016
Endothelial dysfunction in systemic sclerosis
Nezam Altorok1, Yongqing Wang, Bashar Kahaleh
1Division of Rheumatology and Immunology, Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio, USA.
Purpose Of Review:
Microvascular endothelial cells (MVECs) injury is a critical early event in the pathogenesis of systemic sclerosis (SSc). We aim to provide the reader with an update regarding the role of MVECs in the pathogenesis of SSc and the mechanisms for MVECs dysfunction in the disease.
Recent Findings:
Recent evidence confirms the central role for MVECs in the pathogenesis of SSc, and suggests further mechanisms for MVECs injury. The impact of MVECs perturbations in SSc goes beyond the initiation of the vascular disease to include activation of fibroblasts through the release of cytokines and growth factors like connective tissue growth factor that induce an active and aggressive form of fibroblasts. Moreover, recent studies highlighted a more prominent role for epigenetic factors in the pathogenesis of SSc, and suggested defects in the function of progenitor endothelial cells in SSc. Recent reports helped to shed light on the role of antiendothelial cell antibodies in the pathogenesis of SSc, especially purified subsets of these antibodies like anti-ICAM-1 antibodies, and also reported possible mechanisms for defective vascular endothelial growth factor signaling.
Summary:
It is clear that MVECs dysfunction is a key element in the pathogenesis of SSc, but the initial triggers for MVEC dysfunction remain uncharacterized.
Insights
Microvascular endothelial cells (MVECs) dysfunction is central to systemic sclerosis (SSc) pathogenesis. Recent findings reveal MVEC injury impacts fibroblast activation and involves epigenetic factors, anti-endothelial antibodies, and growth factor signaling defects.
Area of Science:
- Vascular Biology
- Immunology
- Rheumatology
Background:
- Microvascular endothelial cells (MVECs) injury is an early event in systemic sclerosis (SSc) pathogenesis.
- Understanding MVEC dysfunction is crucial for SSc research.
Purpose of the Study:
- To update on the role of MVECs in SSc pathogenesis.
- To elucidate mechanisms of MVEC dysfunction in SSc.
Main Methods:
- Review of recent scientific literature.
- Analysis of emerging evidence on MVEC injury mechanisms in SSc.
Main Results:
- MVECs play a central role in SSc, beyond vascular disease initiation.
- MVEC dysfunction contributes to fibroblast activation via cytokines and growth factors.
- Epigenetic factors, progenitor cell defects, anti-endothelial antibodies (e.g., anti-ICAM-1), and impaired VEGF signaling are implicated in SSc pathogenesis.
Conclusions:
- MVEC dysfunction is a key pathogenic element in SSc.
- The initial triggers for MVEC dysfunction in SSc remain unidentified.
