Rheumatology Medical News about pathogenesis of systemic sclerosis;hypoxia

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Hypoxia in the pathogenesis of systemic sclerosis
Arthritis Research & Therapy, 04/24/09

Beyer C et al. - The review presents current knowledge of molecular signalling pathways in response to hypoxia and discusses the role that hypoxia plays in the pathogenesis of systemic sclerosis (SSc).

Main causes of chronic hypoxia in SSc: capillary rarification and disturbed blood flow, and excessive extracellular matrix accumulation
Physiological mechanisms to overcome tissue hypoxia are impaired and dysregulated in SSc
Hypoxia stimulates the production of several ECM proteins in SSc fibroblasts in a time- and concn-dependent manner
Excessive deposition of matrix might impair further the diffusion of oxygen and cause a vicious circle of hypoxia and tissue fibrosis
Currently, there are no specific modulators of HIFs or prolyl hydroxylase domains (PHDs) available for clinical use
Thus, it is not yet possible to target hypoxia selectively in SSc patients
However, because inhibition of TGF-β prevents the induction of extracellular matrix by hypoxia, blocking of TGF-β signalling might be one approach to target at least in part the hypoxia-induced matrix production in SSc

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