The Role of CC-Chemokines in the Regulation of Angiogenesis.
Angiogenesis, the formation of new blood vessels, is critical for survival and in the regenerative response to tissue injury or ischemia. However, in diseases such as cancer and atherosclerosis, inflammation can cause unregulated angiogenesis leading to excessive neovascularization, which exacerbates disease. Current anti-angiogenic therapies cause complete inhibition of both inflammatory and ischemia driven angiogenesis causing a range of side effects in patients. Specific inhibition of inflammation-driven angiogenesis would therefore be immensely valuable. Increasing evidence suggests that the CC-chemokine class promotes inflammation-driven angiogenesis, whilst there is little evidence for a role in ischemia-mediated angiogenesis. The differential regulation of angiogenesis by CC-chemokines suggests it may provide an alternate strategy to treat angiogenesis associated pathological diseases. The focus of this review is to highlight the significant role of the CC-chemokine class in inflammation, versus ischemia driven angiogenesis, and to discuss the related pathologies including atherosclerosis, cancer, and rheumatoid arthritis. We examine the pros and cons of anti-angiogenic therapies currently in clinical trials. We also reveal novel therapeutic strategies that cause broad-spectrum inhibition of the CC-chemokine class that may have future potential for the specific inhibition of inflammatory angiogenesis.
Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia. anisyah.ridiandries@hri.org.au.|Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia. anisyah.ridiandries@hri.org.au.
Anisyah
A
Ridiandries
Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia. joanne.tan@hri.org.au.|Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia. joanne.tan@hri.org.au.
Joanne T M
JT
Tan
Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia. christina.bursill@hri.org.au.|Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia. christina.bursill@hri.org.au.
Christina A
CA
Bursill
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D007511:Ischemia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology
D020533:Angiogenesis Inhibitors; D019742:Chemokines, CC; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
angiogenesis; chemokines; inflammation; ischemia