The role of cytomegalovirus in angiogenesis
Section snippets
Angiogenesis
New blood vessels are formed in response to normal physiological stimuli during fetal development, wound healing, and growth/development. However, neovascularization is also a consequence of numerous pathological conditions such as tumor growth, arthritis and is a prominent feature of vascular diseases like atherosclerosis and transplant associated vasculopathy and chronic allograft rejection. New blood vessels are formed in one of two processes deemed angiogenesis or vasculogenesis. While
Cytomegalovirus in chronic diseases that involve angiogenesis
Human cytomegalovirus (HCMV) is a ubiquitous beta-herpesvirus that persists for the life of the human host following primary infection. Typically, HCMV infection of healthy, immunocompetent hosts results in subclinical disease. However, infection of immunocompromised individuals may cause serious life-threatening disease, which is still a significant problem in congenital disease and in bone marrow transplant recipients. HCMV has been associated with long-term diseases including the vascular
Role of endothelial cells in normal physiology and during CMV infection
Endothelial cells (ECs) are a key cellular component of several physiological processes, such as angiogenesis, regulation of coagulation, tissue homeostasis, inflammation, vessel growth, and are an important site of CMV persistence in the host. ECs differentiate from angioblasts in the embryo (Mikkola and Orkin, 2002) and from endothelial progenitor cell (EPC), mesoangioblasts, multipotent adults progenitor cells, or side-population cells in the adult bone marrow (Luttun et al., 2002, Reyes et
How does CMV promote angiogenesis?
CMV typically infects all of the cell types involved in angiogenesis and vascular disease including ECs, smooth muscle cells, pericytes, fibroblasts, and macrophages and promotes angiogenesis by both direct and indirect mechanisms. In addition, infection at sites proximal to the vessel may promote angiogenesis by releasing angiogeneic factors or by increasing local inflammation (angiogenic factors induced by CMV infection are listed in Table 1). To this end, CMV infection of fibroblasts and EC
Conclusions
HCMV has been implicated in the development of chronic diseases that involve angiogenesis. In this review we highlight the mechanisms by which HCMV can promote angiogenesis and stabilize neovessel formation leading to pathologic angiogenesis. HCMV can promote or enhance all of the stages of angiogenesis (Fig. 1). For example, HCMV infected cells directly induce angiogenesis by secreting VEGF and/or other angiogenic factors (Table 1). HCMV can also activate EC and induce their proliferation; and
Acknowledgements
This work was supported by research grants from the National Institutes of Health to D.N. Streblow (HL 083194), S.L. Orloff (HL 085451) and J.A. Nelson (HL 088603).
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