Nitric oxide and postangioplasty restenosis: pathological correlates and therapeutic potential.
Balloon angioplasty revolutionized interventional cardiology as a nonsurgical procedure to clear a diseased artery of atherosclerotic blockage. Despite its procedural reliability, angioplasty's long-term outcome can be compromised by restenosis, the recurrence of arterial blockage in response to balloon-induced vascular trauma. Restenosis constitutes an important unmet medical need whose pathogenesis has yet to be understood fully and remains to be solved therapeutically. The radical biomediator, nitric oxide (NO), is a natural modulator of several processes contributing to postangioplasty restenosis. An arterial NO deficiency has been implicated in the establishment and progression of restenosis. Efforts to address the restenosis problem have included trials evaluating a wide range of NO-based interventions for their potential to inhibit balloon-induced arterial occlusion. All types of NO-based interventions yet investigated benefit at least one aspect of balloon injury to a naive vessel in a laboratory animal without inducing significant side effects. The extent to which this positive, albeit largely descriptive, body of experimental data can be translated into the clinic remains to be determined. Further insight into the pathogenesis of restenosis and the molecular mechanisms by which NO regulates vascular homeostasis would help bridge this gap. At present, NO supplementation represents a unique and potentially powerful approach to help control restenosis, either alone or as a pharmaceutical adjunct to a vascular device.
Janero
D R
DR
NitroMed, Inc., Bedford, MA 01730, USA. djanero@nitromed.com
Ewing
J F
JF
D000800:Angioplasty, Balloon / Q000009:adverse effects; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D012008:Recurrence
D009569:Nitric Oxide