Nitric oxide-based molecular strategies for restenosis therapy

Abstract

Arterial renarrowing (restenosis) limits balloon angioplasty’s therapeutic potential, despite the benefits of intravascular prosthetic devices called stents. Nitric oxide (NO) mediates/regulates diverse aspects of blood vessel function, and NO insufficiency contributes to many occlusive vascular diseases. Numerous preclinical and more restricted human studies suggest that NO supplementation may help solve the restenosis problem, although the extant data do not conclusively demonstrate that pharmacologic NO prevents clinical restenosis. This article reviews 20 patents from the past three years that claim methods for treating restenosis with NO by using NO-releasing polymers, small-molecule NO donors, and nitric oxide synthase (NOS)-based molecular approaches. The authors suggest that a controlled-release delivery platform capable of extending the intrinsically short half-life of NO, and comprised of a stent coated with a stable, biocompatible polymer containing a low-molecular-weight NO donor represents a most promising, state-of-the-art approach for treating restenosis with NO. The expanding clinical applications of angioplasty, the persistence of the restenosis problem, and the critical role of NO in maintaining arterial patency and homeostasis will undoubtedly elicit further inventions for NO-based restenosis therapy.

Keywords::

• angioplasty
• atherosclerosis
• device coating
• endothelial dysfunction
• inflammation
• nitric oxide (NO)
• restenosis
• stent