Elsevier

Autoimmunity Reviews

Volume 14, Issue 4, April 2015, Pages 314-322
Autoimmunity Reviews

Review
Vascular biomarkers and correlation with peripheral vasculopathy in systemic sclerosis

https://doi.org/10.1016/j.autrev.2014.12.001Get rights and content

Highlights

  • Peripheral vasculopathy determines a considerable burden in systemic sclerosis.

  • Several vascular mediators are dysregulated in systemic sclerosis.

  • Some vascular biomarkers correlate with capillaroscopic changes and digital ulcers.

  • Vascular mediators could become targets for novel specific therapies.

Abstract

Vascular disease is a hallmark of systemic sclerosis (SSc). It is present in every patient, being responsible both for the earliest clinical manifestations and the major life-threatening complications of the disease, and thus determining important morbidity and mortality.

In SSc, progressive vascular injury leads to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and chronic hypoxia. These phenomena are often accompanied by abnormal levels of vascular factors.

Microangiopathy in SSc may be easily assessed by nailfold videocapillaroscopy. The variety of derangements detected in the nailfold capillaries is accompanied by abnormal levels of different vascular mediators and appears to be the best evaluable predictor of the development of peripheral vascular complications, such as digital ulcers.

The purpose of this review is to summarize in SSc the most relevant vascular biomarkers and the main associations between vascular biomarkers and capillaroscopic parameters and/or the presence of digital ulcers. Vascular biomarkers could become useful predictive factors of vascular damage in SSc, allowing an earlier management of vascular complications.

Section snippets

Introduction—systemic sclerosis is a vascular disease from its early onset

Systemic sclerosis (SSc; scleroderma) is a life-threatening connective tissue disorder of unknown etiology, characterized by widespread vascular injury and dysfunction, impaired angiogenesis, immune dysregulation and progressive fibrosis of the skin and numerous visceral organs [1], [2], [3], [4].

A growing body of evidence supports the concept that SSc is primarily a vascular disease mediated by autoimmunity and evolving into tissue fibrosis [5], [6]. The dysregulation of vascular tone control,

Nailfold videocapillaroscopy: an open-window for detecting microvasculopathy in SSc

The damage of the microvessels evolves progressively from the early to the late stages in SSc, with different morphological abnormalities that are clearly shown by nailfold videocapillaroscopy (NVC) changes during the disease evolution [14], [15], [16], [17], [18]. These modifications are often accompanied by abnormal levels of angiogenic/angiostatic factors and markers of EC activation and injury.

The variety of NVC changes parallel the different degree of vascular disturbances in SSc [6], [9].

Vascular biomarkers and correlations with NVC changes and DUs

Several vascular biomarkers have been studied in SSc and correlated with NVC changes and the presence of DUs (Table 2, Fig. 1).

Conclusion

Microvascular abnormalities are the earliest events and key features of SSc responsible for the clinical manifestations of peripheral vasculopathy that are among the major life-threatening complications of the disease.

SSc microangiopathy seems to be strictly related to an impairment of selective factors reflecting disturbances of angiogenesis and endothelium damage. Many of these markers have been shown to clinically correlate with disturbed NVC capillary architecture and/or the occurrence of

Take-home messages

  • In SSc, microvascular abnormalities are responsible both for the earliest clinical manifestations of peripheral vasculopathy and the major life-threatening complications of the disease.

  • Several vascular mediators are dysregulated in SSc, reflecting endothelial damage and disturbances of angiogenesis.

  • Some of these biomarkers correlate with NVC changes and/or the occurrence of ischemic DUs.

  • Vascular mediators and their pathways could become targets for novel specific therapies, aiming to prevent

Acknowledgments

IC is supported by a research grant from the Foundation for the Development of Internal Medicine in Europe (FDIME). IC acknowledges Dr. Paula Vaz Marques for the NVC pictures.

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      Citation Excerpt :

      It increased concentrations were strongly associated with avascular areas and tended to be elevated in patients with “Late” NVC pattern. This is in accordance with several studies that have reported markedly increased VEGF in SSc skin and serum despite clear evidence of an insufficient angiogenic response (Avouac et al., 2013; Choi et al., 2003; Chora et al., 2015; Distler et al., 2002, 2004; Mackiewicz et al., 2002; Manetti et al., 2010). This is also in agreement with notion of inverse correlation between serum VEGF levels and capillary density with significantly higher VEGF concentrations in SSc patients with the “Late” NVC pattern, compared to patients with the “Early” or “Active” NVC patterns reported by other authors (Avouac et al., 2013; Choi et al., 2003).

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