A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions.
BACKGROUND
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. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp298 variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions.


METHODS
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.


RESULTS
Collateral development was lower in patients carrying the Asp298 variant 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 Asp298 variant (p = 0.03) while the Asp298 variant was the sole variable independently associated with the recipient filling grade (p = 0.03).


CONCLUSIONS
Collateral development is lower in patients with the Asp298 variant. This may be explained by the decreased NOS activity in patients with the Asp298 variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development.
Lamblin
Nicolas
N
Hôpital Cardiologique, Centre Hospitalier Universitaire de Lille, Place de Verdun, 59037 Lille cedex, France. nicolas.lamblin@pasteur-lille.fr
Cuilleret
François J
FJ
Helbecque
Nicole
N
Dallongeville
Jean
J
Lablanche
Jean-Marc
JM
Amouyel
Philippe
P
Bauters
Christophe
C
Van Belle
Eric
E
D002908:Chronic Disease; D003097:Collateral Circulation / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012737:Sex Factors; D012907:Smoking
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III