Effect of Homocysteine-Lowering B Vitamin Treatment on Angiographic Progression of Coronary Artery Disease: A Western Norway B Vitamin Intervention Trial (WENBIT) Substudy

Løland, Kjetil Halvorsen; Bleie, Øyvind; Blix, Are J.; Strand, Elin; Ueland, Per Magne; Refsum, Helga; Ebbing, Marta; Nordrehaug, Jan Erik; Nygård, Ottar

doi:10.1016/j.amjcard.2010.01.019

Cited by 41 publications

(37 citation statements)

References 30 publications

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“…Although folate and vitamin B12 supplementation are used to lower Hcy levels, such treatment can potentially cause harmful effects, especially in patients with HHcy. 36, 37 In light of our findings, therapeutic approaches to modulate SHP activity could be envisioned for the treatment of HHcy caused by Hcy metabolic dysregulation.…”

Section: Resultsmentioning

confidence: 82%

Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice

et al. 2015

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BACKGROUND & AIMS Hyperhomocysteinemia is often associated with liver and metabolic diseases. We studied nuclear receptors that mediate oscillatory control of homocysteine homeostasis in mice. METHODS We studied mice with disruptions in Nr0b2 (called SHP-null mice) Bhmt, or both genes (BHMT-null/SHP-null mice), along with mice with wild-type copies of these genes (controls). Hyperhomocysteinemia was induced by feeding mice alcohol (the NIAAA binge model) or chow diets along with water containing 0.18% DL-homocysteine. Some mice were placed on diets containing cholic acid (1%) or cholestyramine (2%), or high-fat diets (60%). Serum and livers were collected over a 24 hr light–dark cycle and analyzed by RNA-seq, metabolomic, and quantitative PCR, immunoblot, and chromatin immunoprecipitation assays. RESULTS SHP-null mice had altered timing in expression of genes that regulate homocysteine metabolism, compared with control mice. Oscillatory production of S-adenosylmethionine, betaine, choline, phosphocholine, glyceophosphocholine, cystathionine, cysteine, hydrogen sulfide, glutathione disulfide, and glutathione, differed between SHP-null mice and control mice. SHP inhibited transcriptional activation of Bhmt and Cth by FOXA1. Expression of Bhmt and Cth was decreased when mice were fed cholic acid but increased when they were placed on diets containing cholestyramine or high-fat content. Diets containing ethanol or homocysteine induced hyperhomocysteinemia and glucose intolerance in control but not SHP-null mice. In BHMT-null and BHMT-null/SHP-null mice fed a control liquid, lipid vacuoles were observed in livers. Ethanol feeding induced accumulation of macrovesicular lipid vacuoles to the greatest extent in BHMT-null and BHMT-null/SHP-null mice. CONCLUSIONS Disruption of Shp in mice alters timing of expression of genes that regulate homocysteine metabolism and the liver responses to ethanol and homocysteine. SHP inhibits the transcriptional activation of Bhmt and Cth by FOXA1.

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Section: Resultsmentioning

confidence: 82%

Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice

et al. 2015

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“…The length of follow-up was on average less than one year and might have been too short to detect a relation between atherosclerosis progression and vitamin D status. However, we observe significant progression of atherosclerosis over time in this cohort and have previously associated atherosclerosis progression in this subgroup with the folic acid treatment 18 and plasma levels of methylated amino acids. 19 The average 25OHD3 concentration was 64 nmol/l (26 ng/ml) and only 3.8% and 24% of the participants had concentrations below suggested cut-offs for deficiency (30 nmol/l) and inadequacy (50 nmol/l), respectively.…”

Section: Strengths and Limitationsmentioning

confidence: 77%

“…18 From baseline to follow-up there was a decrease (p < 0.001) in mean AE SD MLD from 1.92 AE 0.55 to 1.75 AE 0.51 mm and an increase in DS (p < 0.001) from 37.6 AE 9.64 to 42.0 AE 10.4 percentage points for all lesions. Table 4 shows the linear quantile regression analysis for all lesions combined.…”

Section: Progression Of Cadmentioning

confidence: 89%

Vitamin D status was not associated with ‘one-year’ progression of coronary artery disease, assessed by coronary angiography in statin-treated patients

Degerud

Løland

Nygård

et al. 2014

Eur J Prev Cardiolog

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“…After a mean follow-up of 7.3 years, there was no difference observed between the active treatment and placebo groups with respect to any cardiovascular outcome [34]. These negative findings were confirmed in a randomized trial involving Norwegian patients and in the Western Norway B Vitamin Intervention Trial [35,36]. Another study attempted to determine if the failure of B vitamins occurred as a result of missing cofactors.…”

Section: Contemporary Clinical Trials Of Antioxidants and Cardiovascumentioning

confidence: 99%

Antioxidants and coronary artery disease

Leopold

2015

Coronary Artery Disease

113

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Oxidant stress in the cardiovascular system may occur when antioxidant capacity is insufficient to reduce reactive oxygen species and other free radicals. Oxidant stress has been linked to the pathogenesis of atherosclerosis and incident coronary artery disease. As a result of this connection, early observational studies focused on dietary antioxidants, such as β-carotene, α-tocopherol, and ascorbic acid, and demonstrated an inverse relationship between intake of these antioxidants and major adverse cardiovascular events. These findings supported a number of randomized trials of selected antioxidants as primary and secondary prevention to decrease cardiac risk; however, many of these studies reported disappointing results with little or no observed risk reduction in antioxidant treated patients. Several plausible explanations for these findings have been suggested, including incorrect antioxidant choice or dose, synthetic versus dietary antioxidant as the intervention, and patient selection, all of which will be important to consider when designing future clinical trials. This review will focus on the contemporary evidence that is the basis for our current understanding of the role of antioxidants in cardiovascular disease prevention.

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Effect of Homocysteine-Lowering B Vitamin Treatment on Angiographic Progression of Coronary Artery Disease: A Western Norway B Vitamin Intervention Trial (WENBIT) Substudy

Cited by 41 publications

References 30 publications

Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice

Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice

Vitamin D status was not associated with ‘one-year’ progression of coronary artery disease, assessed by coronary angiography in statin-treated patients

Antioxidants and coronary artery disease

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