Angiogenesis in Chronic Inflammation

The putative role of angiogenesis in chronic inflammatory diseases is the maintenance of the inflammatory state by allowing ongoing recruitment of inflammatory cells and by supplying nutrients and oxygen to proliferating inflamed tissue. The increased endothelial surface creates an enormous capacity for the production of cytokines, adhesion molecules, and other inflammatory stimuli [35]. 

In many chronic inflammatory diseases, angiogenesis can be identified in the inflamed lesions. For example, in rheumatoid arthritis extensive neovascularization is present in the inflamed synovium where it is one of the earliest histopathological findings [36]. Since in RA synoviocytes exhibit characteristics of tumour cells, including somatic mutations in key regulatory genes such as H-ras and the p53 tumour suppressor, RA can be viewed as a multicentric tumour-like mass that invades and destroys its local environment [37]. Concurrent increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis. 

Although the identity of the factors that promote angiogenesis in RA specifically still remain unclear, both synovial tissue and fluid are enriched in angiogenesis-promoting factors. These include cytokines such as bFGF, VEGF, and IL-8, and soluble VCAM-1 and E-selectin [38]. 

In other chronic inflammatory diseases elevated levels of angiogenic factors were also found. In patients with psoriasis, skin lesions over-expressed IL-8 while the expression of one of the inhibitors of angiogenesis, thrombospondin-1, was downregulated [39]. 

Neovascularization in artherosclerotic lesions may be regulated by VEGF, as this factor is over-expressed by different cells in the plaque tissue [40-42]. The increased serum levels of VEGF that correlate with disease activity in patients with Crohn s disease and ulcerative colitis, indicate a role for this cytokine in promoting inflammation. Most likely, increased vascn-lar permeability and/or wound healing via its pro-angiogenic activity are the basis for this effect [43]. 

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Aconitine, meaconitine, and hypaconitine are more potent than, and aconite extracts are equipotent to, hydrocortisone and infomethacin in inhibiting angiogenesis in chronic inflammation [92]. Aconitine stimulate the response to interferon-y-activated expression of MHC class II (la antigen) by macrophages, which is induced by increasing the plasma corticosterone level in mice [93]. 

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