title: Healing arterial ulcers: Endothelial lining regeneration upon vascular denudation injury.
abstract: Thrombosis and restenosis are the most prevalent late complications of coronary artery stenting. Current standards of clinical care focus on prevention of smooth muscle cell proliferation by the use of drug-eluting stents able to release anti-proliferative drugs. Unfortunately, these drugs also block endothelial cell proliferation and, in this manner, prevent recovery of endothelial cell coverage. Continued lack of endothelial repair leaves the root cause of thrombosis and restenosis unchanged, creating a vicious cycle where drug-mediated prevention of restenosis simultaneously implies promotion of thrombosis. In this issue of Vascular Pharmacology, Hussner and colleagues provide in vitro evidence and a mechanistic basis for the use of atorvastatin in stents as a way to bypass this roadblock. Here we review the pathological mechanisms and therapeutic approaches to restore flow in occluded arteries. We argue that rational design of drug eluting stents should focus on specific inhibition of smooth muscle cell proliferation with concurrent stimulation of endothelial regeneration. We comment on the current poor understanding of the cellular and molecular regulation of endothelial cell proliferation in the context of a functional artery, and on the pitfalls of extrapolating from the well-studied process of neovascularization by sprouting vessel formation.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Austin I
authors.initials: AI
authors.lastname: McDonald
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.. Electronic address: arispe@mcdb.ucla.edu.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology*; D049109:Cell Proliferation / Q000502:physiology; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D012038:Regeneration / Q000502:physiology*; D014456:Ulcer / Q000473:pathology*; D057772:Vascular System Injuries / Q000473:pathology*; D014945:Wound Healing / Q000502:physiology*
keywords: Endothelial regeneration; Restenosis; Stenosis; Thrombosis; Vascular injury