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<p>Abstract</p> <p>Background</p> <p>Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. <it>In vitro </it>and <it>in vivo </it>studies have suggested a decreased NOS activity in patients with the Asp²⁹⁸variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions.</p> <p>Methods</p> <p>We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques.</p> <p>Results</p> <p>Collateral development was lower in patients carrying the Asp²⁹⁸variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 ± 0.08 and 2.89 ± 0.08, respectively, p = 0.04; recipient filling grade: 3.00 ± 0.08 and 3.24 ± 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp²⁹⁸variant (p = 0.03) while the Asp²⁹⁸variant was the sole variable independently associated with the recipient filling grade (p = 0.03).</p> <p>Conclusion</p> <p>Collateral development is lower in patients with the Asp²⁹⁸variant. This may be explained by the decreased NOS activity in patients with the Asp²⁹⁸variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development.</p>