Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease

2008 ◽  
Vol 294 (5) ◽  
pp. H1971-H1977 ◽  
Author(s):  
An L. Moens ◽  
Christiaan J. Vrints ◽  
Marc J. Claeys ◽  
Jean-Pierre Timmermans ◽  
Hunter C. Champion ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Folic Acid ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Therapeutic Potential ◽  
Antithrombotic Effects ◽  
B Vitamin ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Folic acid (FA) is a member of the B-vitamin family with cardiovascular roles in homocysteine regulation and endothelial nitric oxide synthase (eNOS) activity. Its interaction with eNOS is thought to be due to the enhancement of tetrahydrobiopterin bioavailability, helping maintain eNOS in its coupled state to favor the generation of nitric oxide rather than oxygen free radicals. FA also plays a role in the prevention of several cardiac and noncardiac malformations, has potent direct antioxidant and antithrombotic effects, and can interfere with the production of the endothelial-derived hyperpolarizing factor. These multiple mechanisms of action have led to studies regarding the therapeutic potential of FA in cardiovascular disease. To date, studies have demonstrated that FA ameliorates endothelial dysfunction and nitrate tolerance and can improve pathological features of atherosclerosis. These effects appear to be homocysteine independent but rather related to their role in eNOS function. Given the growing evidence that nitric oxide synthase uncoupling plays a major role in many cardiovascular disorders, the potential of exogenous FA as an inexpensive and safe oral therapy is intriguing and is stimulating ongoing investigations.

Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis

2008 ◽  
Vol 294 (5) ◽  
pp. E978-E986 ◽  
Author(s):  
Elena Galluccio ◽  
PierMarco Piatti ◽  
Lorena Citterio ◽  
Pietro C. G. Lucotti ◽  
Emanuela Setola ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Stent Restenosis ◽  
Nos3 Gene ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
In Stent Restenosis

Little is known about the association of endothelial nitric oxide synthase (NOS3) gene polymorphisms and the presence of insulin resistance and the early evolution of atherosclerosis in nondiabetic subjects with cardiovascular disease (CAD) and stent implantation. The present study was performed in an attempt to better understand whether metabolic, endothelial, and angiographic findings characteristic of subjects with cardiovascular disease and in-stent restenosis are related to NOS3 variants. This is a case-control study performed from 2002 to 2006. All subjects admitted to the study were recruited in the Nord-Centre of Italy, most from Milan and its surrounding towns. Measures of glucose tolerance, insulin sensitivity, markers of endothelial dysfunction, forearm vasodilation, and adipokine levels were determined and associated to the frequency of two single-nucleotide polymorphisms of NOS3, i.e., Glu298Asp (rs1799983, G/T) and rs753482 (intron 18 A/C). A total of 747 subjects, not known to have diabetes, were evaluated: 333 subjects had asymptomatic CAD, 106 subjects had unstable angina and were evaluated for in-stent restenosis 6 mo after stent placement, and 308 were control subjects. The presence of TT and CC minor alleles was significantly greater in case groups compared with control subjects. At phenotypic level, subjects with the polymorphisms were characterized by hyperinsulinemia and reduced reactive hyperemia, whereas increased leptin and decreased adiponectin levels were present in subjects with restenosis in the presence of reduced minimal lumen diameter and length of stenosis almost doubled. Hyperinsulinemia, endothelial dysfunction, and a more atherogenic profile seem to be peculiar features of subjects with asymptomatic CAD and restenosis carrying NOS3 gene variants.

scholarly journals Folic acid reduces doxorubicin-induced cardiomyopathy by modulating endothelial nitric oxide synthase

2017 ◽  
Vol 21 (12) ◽  
pp. 3277-3287 ◽  
Author(s):  
Yanti Octavia ◽  
Georgios Kararigas ◽  
Martine de Boer ◽  
Ihsan Chrifi ◽  
Rinrada Kietadisorn ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Folic Acid ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Modulating Endothelial Nitric Oxide Synthase by Folic Acid Reduces Doxorubicin-Induced Cardiotoxicity and Mortality

2012 ◽  
Vol 53 ◽  
pp. S171
Author(s):  
Yanti Octavia ◽  
Melissa Swinnen ◽  
Georgios Kararigas ◽  
Rinrada Kietadisorn ◽  
Daniela Fliegner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Folic Acid ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review

2006 ◽  
Vol 164 (10) ◽  
pp. 921-935 ◽  
Author(s):  
Juan P. Casas ◽  
Gianpiero L. Cavalleri ◽  
Leonelo E. Bautista ◽  
Liam Smeeth ◽  
Steve E. Humphries ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Disease ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Polymorphisms ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Tetrahydrobiopterin rescues impaired responses of cerebral resistance arterioles during type 1 diabetes

2016 ◽  
Vol 14 (1) ◽  
pp. 33-39 ◽  
Author(s):  
William G Mayhan ◽  
Denise M Arrick
Keyword(s):  
Nitric Oxide ◽  
Type 1 Diabetes ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Therapeutic Potential ◽  
Diabetic Rats ◽  
Cerebral Arterioles ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Our goal was to test the hypothesis that administration of tetrahydrobiopterin (BH4) would improve impaired endothelial nitric oxide synthase–dependent dilation of cerebral arterioles during type 1 diabetes. In addition, we examined the influence of BH4 on levels of superoxide in brain tissue. In vivo diameter of cerebral arterioles in nondiabetic and diabetic rats was measured in response to endothelial nitric oxide synthase–dependent agonists (acetylcholine and adenosine 5′-diphosphate) and an endothelial nitric oxide synthase–independent agonist (nitroglycerine) before and during application of BH4 (1.0 µM). We also measured levels of superoxide from cortex tissue in nondiabetic and diabetic rats under basal states and during BH4. Acetylcholine and adenosine 5′-diphosphate dilated cerebral arterioles in nondiabetic rats, but this vasodilation was significantly impaired in diabetic rats. In contrast, nitroglycerine produced similar vasodilation in nondiabetic and diabetic rats. Application of BH4 did not enhance vasodilation in nondiabetic rats but improved impaired cerebral vasodilation in diabetic rats. Basal superoxide levels were increased in cortex tissue from diabetic rats, and BH4 reduced these levels to that found in nondiabetic rats. Thus, BH4 is an important mediator of endothelial nitric oxide synthase–dependent responses of cerebral arterioles in diabetes and may have therapeutic potential for the treatment of cerebral vascular disease.

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