Role of the endothelium in modulating neointimal formationVasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions

Abstract

Restenosis at the site of an endoluminal procedure remains a significant problem in the practice of interventional cardiology. We present current data on intimal hyperplasia, which identify the major role of endothelial cells (ECs) in the development of restenosis. Considering endothelial denudation as one of the most important mechanisms contributing to restenosis, we focus more attention on methods of accelerating restoration of endothelial continuity. Prevention of restenosis may be achieved by promoting endothelial regeneration through the use of growth factors, EC seeding, vessel reconstruction with autologous EC/fibrin matrix, and the use of estrogen-loaded stents and stents designed to capture progenitor ECs.

The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

“…This relationship has also been validated in humans (11). The endothelium normally provides a nonpermeable barrier to protect VSMCs against the effect of circulating growth factors (12). The endothelium also produces nitric oxide, which has several antimitogenic properties (13,14).…”

“…Within the first three days after PCI, mural thrombus forms along the injured vessel wall and on the stent struts in the porcine coronary artery model (12,15). The amount of thrombus is proportional to the extent of arterial wall injury (12).…”

“…The amount of thrombus is proportional to the extent of arterial wall injury (12). Although unproved, a direct relationship may exist between the absolute amount of thrombus and the subsequent neointimal hyperplasia (15).…”

“…Vessel wall overstretching during PCI may also induce an inflammatory response by stimulating infiltration of inflammatory leukocytes into the adventitia (22). Experimental studies have shown that the degree of inflammation and subsequent neointima formation is proportional to the degree of penetration of the stent struts into the vessel wall (12). Moreover, a foreign body immune response directed against the stent struts has been shown in a porcine model of coronary artery injury (23,24) and in humans (25).…”

“…Estradiol may improve vascular healing, decrease proliferation and migration of SMCs and induce local angiogenesis (12). Beside its beneficial impact on the lipid profile, estrogen stimulates nitric oxide production by endothelial cells (139,140).…”