Systemic Sclerosis

An Update

Uwe-Frithjof Haustein, MD, PhD


Lab Med. 2011;42(9):562-572. 

In This Article

Endothelial-derived Proteins With Pathophysiological Relevance


Increased plasma endothelin levels have been associated with Raynaud's phenomenon and SSc, particularly diffuse SSc.[46] Endothelin exerts a prolonged vasoconstriction and is fibrogenic as well, enhancing FB proliferation and collagen synthesis.[46] Thus, it may be a major link between vascular pathology and the abundant deposition of connective tissue matrix materials in SSc. Increased endothelin expression in microvascular EC of the upper dermis in association with an increased number of endothelin-binding sites is also reported in SSc.[44]

Angiotensin-Converting Enzyme

Angiotensin-converting enzyme is located on the luminal surface of the endothelium. Decreased plasma ACE activity has been reported in SSc patients.[47] Angiotensin-converting enzyme levels are inversely related to levels of von Willebrand factor (vWF) and have been proposed as markers of EC injury. Further indicators of vascular injury include increased serotonin-induced platelet aggregation. In addition, platelets release thromboglobulin, platelet factor 4, cytokines, and growth factors (PDGF and TGF) that can themselves activate EC. This indicates an imbalance between endothelial and platelet function.


In SSc, EC expressing increased numbers of ligands of 1-integrins as well as various cell adhesion molecules such as MadCAM1, CD34, ELAM-1, and intercellular adhesion molecule (ICAM)-1 facilitate the interaction with lymphocytes expressing 1- and 2- integrins.[48] In this way the transcapillary migration of inflammatory cells is enhanced, leading to prominent T cell infiltrates around blood vessels in early skin lesions.[49] The ACEA also induce leukocyte adhesion to EC.[35] Circulating levels of endothelin-1, P-selectin, E-selectin (E-sel), vascular cell adhesion molecule (VCAM)-1, and ICAM-1 are useful markers of vascular and fibrotic change in SSc.[50] They correlate well with their in situ activity.[51]


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