Endothelial Nitric Oxide Synthase T-786C Mutation, A Reversible Etiology of Prinzmetal's Angina Pectoris

Glueck, Charles J.; Munjal, J.; Khan, Ayub; Umar, Muhammad; Wang, Ping

doi:10.1016/j.amjcard.2009.10.062

Cited by 19 publications

(37 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 43 cases with well-documented PVA, we previously reported [10] that the mutant eNOS T-786C allele frequency in patients was 29% vs. 14% in 43 healthy normal controls (p = 0.016). In 19 patients with persistent angina symptoms despite conventional nitrate-calcium channel blocker therapy, on treatment with 9 g/day L-arginine to increase NO production, 10 (53%) became angina-free, 3 (16%) were improved but not angina free, and 6 (32%) had no change in their angina.…”

Section: Introductionmentioning

confidence: 92%

“…Fifty-nine not previously reported [10,11] patients with PVA and intractable angina despite conventional calcium channel blockernitrate therapy were studied in the sequence of their referral by their cardiologists and physicians. The diagnosis of PVA was confirmed by transient ST elevation during angina attacks at rest in patients with normal coronary angiography, or by ergonovine or acetylcholine-induced coronary vasospasm during coronary angiography.…”

Section: Casementioning

confidence: 99%

“…Deficient release of nitric oxide (NO) is an important factor in the pathogenesis of CAS [8] in PVA [4,[9][10][11]. A thymine replacement by cytosine at nucleotide -786 of the endothelial NO synthase (eNOS) gene reduces eNOS gene promoter activity and reduces levels of the potent coronary artery vasodilator, NO [12].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The eNOS T786C mutation, Prinzmetal's Variant Angina, and amelioration of angina by l-arginine in 59 patients with intractable angina despite calcium channel blocker–nitrate therapy

Glueck

Prince

Shah

et al. 2015

IJC Metabolic & Endocrine

Self Cite

View full text Add to dashboard Cite

a b s t r a c tBackground: Despite calcium channel blockers -long acting nitrates (CaCH-LAN),~20% of patients with Prinzmetal's Variant Angina (PVA) retain intractable angina. The endothelial nitric oxide synthase (eNOS) T-786C polymorphism, more common in PVA than normal subjects, decreases the conversion of L-arginine to nitric oxide (NO), promoting coronary artery spasm (CAS)-angina. Methods: PCR measures for the eNOS T-786C polymorphism were done in 59 PVA patients with intractable angina despite CaCH-LAN. Using the Seattle Angina Questionnaire (SAQ), effects of 9 g L-arginine/day were prospectively assessed in 28 patients with ≥3 visits, pre-treatment entry and ≥2 follow-ups at 1 and 5 months, and in 31 additional patients with 2 visits, entry and 7.7 months on L-arginine. This allowed an assessment of response to L-arginine in 59 patients at entry and 12 months later (last follow-up). Results: In the cohort of 59 patients, 47% of eNOS alleles were mutant vs. 20% in 72 normal controls, p b .0001. Compared to pre-treatment baseline, all 5 SAQ components improved in 28 patients at 1 (p ≤ .02 for all) and 5 months (p ≤ .03 for all) on L-arginine treatment, and improved in the 59 patients after 12 months on L-arginine, p ≤ .002 for all. The eNOS mutation was a significant positive independent determinant of reduction in anginal symptoms, p = .0002. Patients hetero-and homozygous for the eNOS mutation had greater improvement in anginal symptoms. Conclusions: In patients with intractable angina despite CaCH-LAN, the eNOS T-786C mutation appears to facilitate CAS via reduced NO production, a condition susceptible to treatment with L-arginine.

show abstract

Section: Introductionmentioning

confidence: 92%

Section: Casementioning

confidence: 99%

See 1 more Smart Citation

The eNOS T786C mutation, Prinzmetal's Variant Angina, and amelioration of angina by l-arginine in 59 patients with intractable angina despite calcium channel blocker–nitrate therapy

Glueck

Prince

Shah

et al. 2015

IJC Metabolic & Endocrine

Self Cite

View full text Add to dashboard Cite

show abstract

“…(2) In addition, endothelial nitric oxide synthase T-786C mutation has been associated with increased coronary artery basal tone due to a reduction in nitric oxide production. (10) This, in turn, increases vessel susceptibility to vasoconstrictors such as acetylcholine and predisposition to coronary artery vasospasm. (10,11) There appears to be a higher incidence of PVA in Asian countries as opposed to Caucasian populations.…”

Section: Discussionmentioning

confidence: 99%

“…(10) This, in turn, increases vessel susceptibility to vasoconstrictors such as acetylcholine and predisposition to coronary artery vasospasm. (10,11) There appears to be a higher incidence of PVA in Asian countries as opposed to Caucasian populations. (2)(3)(4)12) Miwa et al demonstrated a positive result in 93% of Japanese patients who underwent provocation testing, (13) while a prevalence of 74% was found in a Taiwanese population.…”

Section: Discussionmentioning

confidence: 99%