Abstract

Angioplasty aiming at vascular dilatation causes endothelial denudation and induces complex inflammatory responses that affect vascular healing, including delayed reendothelialization and excessive neointima proliferation. Resveratrol is known for multiple beneficial effects on the vessel wall after systemic treatment or sustained release from a stent. It is also used as an additive on drug-coated balloon catheters (DCB). In this study, the effect of a single dose of resveratrol, three days to four weeks after administration as a balloon coating during angioplasty, was investigated. Sixteen pigs underwent angioplasty with resveratrol-coated or uncoated balloon catheters in coronary and peripheral arteries. Vessels were overstretched by approximately 20% to enhance vessel wall injury and to produce persistent vessel wall irritation. A significantly reduced number of micro vessels and macrophages in the adventitia, as well as an improved reendothelialization of the vessel lumen, were observed in resveratrol-treated peripheral arteries. The coronaries had a much higher injury score compared to peripheral vessels. Resveratrol-dependent reduction of macrophages, micro vessels or acceleration of reendothelialization was not evident in the coronary vessels. Additionally, no significant effect on neointima proliferation and inflammation score in either vessel territory was observed as a result of resveratrol treatment. In conclusion, the results suggest that resveratrol diminishes the inflammatory response and promotes vascular healing in peripheral arteries. These same effects are absent in more severely injured coronary arteries.

Highlights

  • Balloon angioplasty is a widely used endovascular standard procedure to widen or reopen vessel obstructions to restore blood flow

  • Vessel overstretch and endothelial denudation as a result of balloon angioplasty induce a cascade of biological processes involved in vascular healing and remodeling

  • The beneficial effects on vascular healing in porcine peripheral arteries from resveratrol dry-coated balloon catheters was demonstrated in this study

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Summary

Introduction

Balloon angioplasty is a widely used endovascular standard procedure to widen or reopen vessel obstructions to restore blood flow. Restenosis, characterized by the transdifferentiation and proliferation of vascular smooth muscle cells (VSMCs) and excessive secretion of the extracellular matrix, is one of the most common complications after angioplasty procedures. Cytostatic drugs, such as paclitaxel, are the current “gold standard” in restenosis prophylaxis and target VSMC proliferation. The benefits on vascular healing using a local single-dose administration of resveratrol as a balloon coating has not yet been tested. A porcine model is used to investigate the effect of a local single-dose resveratrol treatment on coronary and peripheral arteries. In vivo data on resveratrol-only coated balloons indicate positive effects of resveratrol on the vessel wall of peripheral arteries, without affecting neointima proliferation. We investigate resveratrol effects on coronary and peripheral arteries at defined time points

Injury Score and Morphometry
Inflammation Score and Fibrin Score
Vasa Vasorum Neovascularization
Macrophages
Discussion
Angioplasty Balloon Catheters and Coating Procedure
Animal Experiments
Histochemistry and Morphometry
Immunohistochemistry
Statistical Analysis
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