Atorvastatin does not impair endothelial cell wound healing in an in vitro model of vascular injury

Percutaneous coronary intervention (PCI) became standard treatment modality for coronary revascularization. However, it is associated with endothelial cell denudation, which may predispose to in-stent thrombosis and restenosis. Since statins may inhibit vascular cell proliferation, one may fear that their early administration will delay post-PCI re- endothelialization. We have therefore employed an in vitro scratch assay to examine how atorvastatin affects endothelial cell wound healing. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and wounded by scraping. Scratch healing in the presence or absence of atorvastatin was monitored by time-lapse photo-microscopy. In addition cells were assessed for viability (MTT assay), migration (chemotaxis chamber), proliferation (³H-thymidine and bromodeoxyuridine incorporation), and cytokine production (immunoassays). The exposure of HUVEC to atorvastatin resulted in a dose-dependent decrease in cell viability and proliferation. However, this effect was observed only at doses ≥1 μM, which is well above the concentrations seen in vivo. At clinically relevant doses (≤0.1 μM) atorvastatin did not impair wound closure, nor did it inhibit cell viability, proliferation, and migration. It did however reduce the constitutive and the stimulated release of cytokines (IL-6, IL-8, MCP-1), adhesion molecules (sICAM-1) and matrix proteins (fibronectin). We conclude that atorvastatin at doses corresponding to concentrations seen in serum during standard therapy does not impair endothelial cell regeneration after injuries mimicking those occurring during PCI. It does, however, inhibits the secretion of pro-inflammatory mediators.