Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011:4:105-25.
doi: 10.2147/JIR.S18145. Epub 2011 Jul 26.

Vascular involvement in systemic sclerosis (scleroderma)

Debendra Pattanaik  1 , Monica Brown, Arnold E Postlethwaite
Affiliations

Vascular involvement in systemic sclerosis (scleroderma)

Debendra Pattanaik et al. J Inflamm Res. 2011.

Abstract

Systemic sclerosis (SSc) is an acquired multiorgan connective tissue disease with variable mortality and morbidity dictated by clinical subset type. The etiology of the basic disease and pathogenesis of the systemic autoimmunity, fibrosis, and fibroproliferative vasculopathy are unknown and debated. In this review, the spectrum of vascular abnormalities and the options currently available to treat the vascular manifestations of SSc are discussed. Also discussed is how the hallmark pathologies (ie, how autoimmunity, vasculopathy, and fibrosis of the disease) might be effected and interconnected with modulatory input from lysophospholipids, sphingosine 1-phosphate, and lysophosphatidic acid.

Keywords: LPA; S1P; autoimmunity; fibrosis; vasculopathy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Autoimmune state develops in a permissive genetic background and is triggered by unknown factors. It results in generation of autoantibodies, autoreactive T cells, and NK cells that can elaborate a host of molecular mediators, cytokines, and growth factors. All these mediators induce vasculopathy and fibrosis (discussed in text). LPA and S1P are generated from aggregated platelets, dendritic cells, mast cells, macrophages, and endothelium. S1P may act as facilitators and promote immune/inflammatory reactions, cardiac and vascular changes, and fibrosis (discussed in text and reviewed in papers by Postlethwaite et al and Postlethwaite11). Abbreviations: AB, antibody; ADCC, antibody dependent cellular cytotoxicity; AECA, anti-endothelial cell antibody; CTGF, connective tissue growth factor; EDA, extra domain A; ET, endothelin; FGF, fibroblast growth factor; IGF, insulin-like growth factor; IL, interleukin; LPA, lysophosphatidic acid; MCP, monocyte chemoattractant protein; MMP, matrix metalloproteinase; NK, natural killer; PAH, pulmonary arterial hypertension; PDGF, platelet-derived growth factor; PDGFR, PDGF receptor; S1P, sphingosine 1-phosphate; TGF, transforming growth factor; T regs, T regulatory cells.
See this image and copyright information in PMC

References

    1. Hochberg M, Silman A, Smolen J, Weinblatt M, Weisman M. Rheumatology. 5th ed. St. Louis: Mosby; 2010. Epidemiology and classification of scleroderma.
    1. Steen VD, Medsger TA., Jr Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum. 2000;43(11):2437–2444. - PubMed
    1. Mayes MD, Trojanowska M. Genetic factors in systemic sclerosis. Arthritis Res Ther. 2007;9(Suppl 2):S5. - PMC - PubMed
    1. Agarwal SK. The genetics of systemic sclerosis. Discov Med. 2010;10(51):134–143. - PMC - PubMed
    1. Arnett FC, Gourh P, Shete S, et al. Major histocompatibility complex (MHC) class II alleles, haplotypes and epitopes which confer susceptibility or protection in systemic sclerosis: analyses in 1300 Caucasian, African-American and Hispanic cases and 1000 controls. Ann Rheum Dis. 2010;69(5):822–827. - PMC - PubMed