Hypoxia—a key regulator of angiogenesis and inflammation in rheumatoid arthritis

S Konisti, S Kiriakidis, EM Paleolog - Nature Reviews Rheumatology, 2012 - nature.com
S Konisti, S Kiriakidis, EM Paleolog
Nature Reviews Rheumatology, 2012nature.com
The importance of inflammation in rheumatoid arthritis (RA) is well understood. This
knowledge has resulted in the development of anti-inflammatory therapies—either broadly
acting (such as steroids) or more specific approaches (such as antibodies against TNF)—
with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA.
However, what is less well appreciated in RA are the links between inflammation, blood-
vessel formation (angiogenesis) and cellular responses to changes in oxygen tension …
Abstract
The importance of inflammation in rheumatoid arthritis (RA) is well understood. This knowledge has resulted in the development of anti-inflammatory therapies—either broadly acting (such as steroids) or more specific approaches (such as antibodies against TNF)—with biologic therapies (including TNF inhibitors) revolutionizing the treatment of RA. However, what is less well appreciated in RA are the links between inflammation, blood-vessel formation (angiogenesis) and cellular responses to changes in oxygen tension. Inadequate oxygenation, termed hypoxia, is thought to drive the increase in synovial angiogenesis that occurs in RA, through expression of hypoxia-inducible molecules, including vascular endothelial growth factor (VEGF). This process promotes further infiltration of inflammatory cells and production of inflammatory mediators, perpetuating synovitis. This Review highlights the molecular pathways activated by hypoxia, and how these pathways might interact with inflammatory signaling to promote and maintain synovitis in RA, with a particular focus on the response of macrophages to hypoxia in the context of RA. Successful treatment of RA, for example with anti-TNF antibodies, reduces levels of proangiogenic factors, including VEGF, and leads to normalization of the vasculature. These processes emphasise the close links between hypoxia, angiogenesis and inflammation in this disease and supports the concept that angiogenesis blockade could be of therapeutic benefit in RA.
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