Biomedical Engineering Reference
In-Depth Information
Coronary Artery Disease
There is compelling evidence that the endothelium is critical to normal coronary
vascular function and that endothelial dysfunction, generally indicated by an
impairment of endothelium-dependent vasodilatation, is an important component
of coronary artery disease (CAD). Endothelial cells synthesize and release a num-
ber of factors, including prostacyclin, NO, endothelium-derived hyperpolarizing
factor, and endothelin, which are important in the regulation of vascular tone and
the control of platelet and leukocyte adhesion, aggregation, and migration. NO
appears to be the critical factor in the preservation of normal coronary vascular
function and there is an established correlation between CAD and an impairment
of NO activity. Thus, to preserve endothelial function, drugs have been used to
either increase the synthesis of NO, or to decrease its breakdown.
The eNOS gene harbors a common polymorphism in intron 4 (4a/b), and some
clinical studies have suggested an association of the rare a-allele with coronary
artery disease and myocardial infarction. However, contradictory results have also
been reported, for example, no significant differences in areas of atherosclerotic
lesions and coronary stenosis percentages were found between men carrying the
a-allele (ba + aa) compared with those homozygous for the b-allele. Subjects with
the a-allele had significantly lower risk of myocardial infarction compared with those
carrying the bb genotype. Men with the a-allele also tended to have coronary
thrombosis less often. The eNOS gene 4a/b polymorphism is not associated with
the extent of coronary atherosclerosis, but the a-allele of the variant seems to protect
to some degree against the development of myocardial infarction.
Role of NO in the Pathophysiology of Angina Pectoris
Coronary artery spasm plays an important role in the pathogenesis of vasospastic
angina, and contributes to the development of several acute coronary syndromes.
eNOS catalyzes the synthesis of NO, which regulates vascular tone, and may be
related to coronary vasospasm. Coronary spasm may be related to particular poly-
morphisms of the eNOS gene. Both a/a and a/b genotypes in intron 4 of eNOS
(NOS4a) are significant predictors of coronary spasm (Kaneda et al.
2006
). In
patients with NOS4a, both the induced and spontaneous contractions are augmented
indicating that NOS4a could be a good biomarker for coronary artery spasm.
Polymorphism of eNOS T-786C gene is associated with reduced NO production
and coronary artery spasm and it might be associated with Prinzmetal's variant
angina. In a study, PCR analyses of eNOS T-786C and stromelysin 5A6A polymor-
phisms were done in white as well as black American women and men with well-
documented Prinzmetal's variant angina and each case was matched with a healthy
control by race and gender (Glueck et al.
2010
). Patients did not differ from con-
trols for the distribution of the stromelysin 6A mutation or for the mutant 6A allele
frequency. Effect of NO-elevating L-arginine was tested on relief of angina in these
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