Vascular Changes in Bleomycin-Induced Scleroderma PDF Print E-mail
Tuesday, 24 January 2012 12:25
Toshiyuki Yamamoto and Ichiro Katayama
Department of Dermatology, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan
Department of Dermatology, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
Received 6 June 2011; Revised 17 August 2011; Accepted 17 August 2011

Systemic sclerosis (SSc) is a connective tissue disease which shows fibrosis of the skin and various internal organs. Although the pathogenesis of SSc has not been fully elucidated yet, it is characterized by vascular injury, immunological abnormalities, and excessive accumulation of extracellular matrix (ECM) proteins in the skin and various internal organs. In particular, systemic vasculopathy plays a fundamental role in SSc and is associated with various altered vascular dysfunctions in the lung, kidney, heart, and skin.

Clinically, Raynaud’s phenomenon, digital ulcers, and abnormal nailfold capillaries are seen in association with peripheral vasculopathy. Raynaud’s phenomenon is caused by vasospasm, commonly seen in patients prior to the onset of sclerodactyly. Endothelial cells have been reported to play an important role in the initial inflammatory as well as subsequent fibrotic process. Histological analysis of the initial stage of scleroderma reveals perivascular infiltrates of mononuclear cells in the dermis, which is associated with increased collagen synthesis in the surrounding fibroblasts. T-cell interaction with vascular endothelial cells may lead to the subsequent cellular immune reaction, which may induce further vascular injury and tissue fibrosis. A number of studies have demonstrated the crucial role of several fibrogenic cytokines released from immunocytes in initiating the sequence of events leading to fibrosis.

Animal models are useful in providing clues for understanding various human diseases and for exploring new treatments. Although animal models which reproduce all the aspects of SSc are not currently available, bleomycin-induced scleroderma mouse exhibits definite dermal sclerosis mimicking human scleroderma. Inthismodel, features such as definite dermal sclerosis with dermal thickening, pulmonary fibrosis, and the presence of autoantibody in the sera are induced; however, vascular alteration in this model has not been remarked. In this paper, insights into the vascular pathogenesis in bleomycin-induced murine model are discussed.

Continue reading the full review paper, by downloading it from the link provided below.

 
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