Angiogenesis and endothelial cell repair in renal disease and allograft rejection.
This review discusses the concept that the turnover and replacement of endothelial cells is a major mechanism in the maintenance of vascular integrity within the kidney. CD133+CD34+KDR+ endothelial cell progenitor cells emigrate from the bone marrow and differentiate into CD34+KDR+ expressing cells, which are present in high numbers within the circulation. These progenitor cells are available for recruitment into normal or inflamed tissues to facilitate endothelial cell repair. In several forms of renal disease, proinflammatory insults mediate oxidative stress, senescence, and sloughing of endothelial cells. A lack of growth factors or an inefficient recruitment of endothelial cell progenitors results in hypoxic tissue injury and accelerates the process of chronic renal failure. Augmentation of vascular repair by the provision of growth factors such as vascular endothelial growth factor or by the transfer of progenitor cells directly into the kidney can be protective and prevent ongoing interstitial damage. In allografts, persistent injury results in excessive turnover of graft vascular endothelial cells. Moreover, chronic damage elicits a response that is associated with the recruitment of both leukocytes and endothelial cell progenitors, facilitating an overlapping process of inflammation and angiogenesis. Because the angiogenesis reaction itself is proinflammatory, this process becomes self-sustaining. Collectively, these data indicate that angiogenesis and endothelial cell turnover are important in renal inflammatory processes and allograft rejection. Manipulation of the response may have therapeutic implications to protect against injury and chronic disease processes.
Division of Nephrology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA.
Marlies E J
ME
Reinders
Ton J
TJ
Rabelink
David M
DM
Briscoe
D000818:Animals; D042783:Endothelial Cells / Q000473:pathology*; D006084:Graft Rejection / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000098:blood supply; D007674:Kidney Diseases / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D009389:Neovascularization, Pathologic; D009393:Nephritis / Q000473:pathology / Q000503:physiopathology; D013234:Stem Cells / Q000473:pathology; D014184:Transplantation, Homologous