Endothelial progenitor cells, neointimal hyperplasia, and hemodialysis vascular access dysfunction: novel therapies for a recalcitrant clinical problem.

Vascular stenosis as a result of neointimal hyperplasia is a major clinical problem that has an impact on multiple and diverse disciplines, including cardiology (coronary restenosis), cardiothoracic and vascular surgery (saphenous vein and polytetrafluoroethylene [PTFE] graft failure), neurology (carotid stenosis), nephrology (dialysis access dysfunction), and transplant medicine (chronic allograft rejection in hearts and kidneys). The traditional response to injury hypothesis on the pathogenesis of neointimal hyperplasia focuses on the migration of medial smooth muscle cells from the media into the intima.1 Recently, there has been a great deal of excitement about the role of circulating smooth muscle progenitor cells in the pathogenesis of neointimal hyperplasia. These cells have been identified in a variety of experimental models of vascular injury,2 and interventions that reduce the number of these cells can attenuate neointimal hyperplasia. In marked contrast to the deleterious effects of smooth muscle progenitor cells on neointimal hyperplasia, circulating endothelial progenitor cells (EPCs) are believed to play an important role in vascular repair and in the inhibition of neointimal hyperplasia.3 See p 12 In this issue of Circulation , Rotmans and colleagues have attempted to achieve the “holy grail” for a vascular access procedure: rapid and complete endothelialization.4 Their experiments are based on a newly developed technique that can coat the surface of stent and graft material with antibodies against CD34 (Orbus Medical Technologies). CD34 is a marker for hematopoietic stem cells, and previous research has demonstrated that coronary stents coated with anti-CD34 have a significant increase in endothelialization as early as 1 hour after deployment because of the binding of circulating CD34+ cells, which then differentiate into endothelial cells.5 Placement of anti-CD34–coated grafts in an arteriovenous model of PTFE graft stenosis by Rotmans et al resulted in almost complete endothelialization of the grafts (both …

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