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Restenosis is associated with decreased coronary artery nitric oxide synthase
P R Myers1, R Webel, V Thondapu
1Department of Medicine, Dalton Cardiovascular Research Center, College of Veterinary Medicine, University of Missouri, Columbia, USA.
Abstract:
The purpose of the present study was to test the hypothesis that restenosis is associated with decreased constitutive nitric oxide synthase activity. Male miniswine with moderately elevated serum cholesterol levels underwent cardiac catheterization and oversized balloon injury to the right and left circumflex coronary arteries, followed 2 weeks later by repeat injury on the same coronary segments. After 4 weeks, the coronary arteries were either immediately frozen in liquid nitrogen or pressure-perfusion fixed and prepared for histologic examination. Constitutive nitric oxide synthase activity was quantified using a fibroblast reporter cell method, while constitutive nitric oxide synthase protein was compared between balloon-injured and non-balloon-injured arteries using Western blot analysis. Immunohistochemical studies were performed using a specific antibody against constitutive nitric oxide synthase protein. Following balloon injury, there was decreased constitutive nitric oxide synthase activity in balloon-injured coronary arteries, compared to distal non-balloon-injured segments from the same artery. Histological examination demonstrated an intact endothelium. Specific antibody staining revealed that there was less constitutive nitric oxide synthase protein reactivity by immunohistochemical analysis. Western analysis confirmed less constitutive nitric oxide synthase protein. The data are consistent with the hypothesis that restenosis is associated with decreased endothelial cell nitric oxide production. The data suggest this is secondary to a decreased amount of constitutive nitric oxide synthase enzyme in the endothelium. A deficiency in constitutive nitric oxide synthase enzyme may contribute to the impaired second messenger and paracrine functions of the endothelium observed during restenosis following balloon injury, including abnormal vasomotion, extracellular matrix formation, and platelet aggregation.
Insights
Restenosis after balloon injury is linked to reduced nitric oxide synthase activity. This decrease in enzyme levels may impair endothelial functions, contributing to restenosis development.
Area of Science:
- Cardiovascular Biology
- Vascular Medicine
- Biochemistry
Background:
- Restenosis is a significant complication following percutaneous coronary interventions.
- Endothelial dysfunction, characterized by impaired nitric oxide (NO) production, is implicated in restenosis.
- Constitutive nitric oxide synthase (cNOS) is the primary source of endothelial NO.
Purpose of the Study:
- To investigate the hypothesis that restenosis is associated with decreased constitutive nitric oxide synthase (cNOS) activity.
- To determine the levels of cNOS protein in balloon-injured versus non-injured coronary artery segments.
Main Methods:
- Male miniswine with hypercholesterolemia underwent balloon angioplasty of coronary arteries.
- cNOS activity was measured using a fibroblast reporter cell assay.
- cNOS protein expression was assessed by immunohistochemistry and Western blot analysis.
Main Results:
- Balloon injury led to a significant decrease in cNOS activity in injured coronary segments compared to non-injured segments.
- Histological examination confirmed an intact endothelium.
- Both immunohistochemistry and Western blot analysis revealed reduced cNOS protein levels in balloon-injured arteries.
Conclusions:
- The study supports the hypothesis that restenosis is associated with diminished endothelial nitric oxide production.
- A decrease in the amount of constitutive nitric oxide synthase enzyme in endothelial cells appears to be the underlying cause.
- Reduced cNOS enzyme may contribute to impaired endothelial functions, such as abnormal vasomotion and increased platelet aggregation, during restenosis.