Hyperhomocyst(e)inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans

Woo, Kam S.; Sanderson, John E.; Sun, Y. Y.; Chook, Ping; Cheung, Annette; Chan, L. T.; Metreweli, C.; Lolin, Y. I.; Celermajer, D.

doi:10.1161/01.cir.101.12.e116

Cited by 141 publications

(166 citation statements)

References 2 publications

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“…13 In cell culture studies, Hcy induced oxidative stress to endothelium 14 and reduced available nitric oxide, a potent vasodilator. 15 Confirming these observations in humans, endothelium-dependent vasodilatation was impaired in temporary 16,17 or chronic 18,19 HHcy.…”

supporting

confidence: 55%

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003–2004)

et al. 2005

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supporting

confidence: 55%

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003–2004)

et al. 2005

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“…Homocysteine may be a marker of endothelial dysfunction (Woo et al, 1997) and thrombotic events (Ridker et al, 1997). The concept of homocysteine being a functional marker of suboptimal folate status has gained popularity (Jacob et al, 1994.…”

Section: Discussionmentioning

confidence: 99%

Folate intake, plasma folate and homocysteine status in a random Finnish population

Alfthan

Laurinen²,

Valsta³

et al. 2003

Eur J Clin Nutr

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Objective: To assess the folate status of Finnish adults using plasma folate and homocysteine as biomarkers and to evaluate dietary and supplementary folate intakes. Materials and methods: Plasma folate, vitamin B 12 and total homocysteine (tHcy) were determined in a random sample of 643 subjects aged 25 -74 y living in the Helsinki area. The methylenetetrahydrofolate reductase (MTHFR)-genotypes were analyzed from a subsample (n ¼ 394). Dietary intake data by 24 h recall and use of vitamin supplements were collected. Results: Plasma folate was normal ( ! 5 nmol=l) in 99% of subjects and optimal ( ! 8 nmol=l) in terms of a minimum tHcy in 90%. Mean plasma folate of non-supplement users was 13.7 and 12.9 nmol=l and tHcy 11.3 and 9.2 mmol=l for men and women, respectively. Elevated tHcy ( > 14 mmol=l) was found in 11% of subjects. Homozygote frequency for MTHFR genotype TT was 5.0% and their plasma tHcy was 14.8 mmol=l compared to the mean of the other subjects, 10.5 mmol=l, P < 0.05. The mean dietary folate intake was 241 mg=day (29 mg=MJ of energy) for men and 205 mg=day (33 mg=MJ) for women, respectively. The main dietary sources of folate were vegetables 12%, wholemeal ryebread 11%, fruits 10%, and potato 10%. Regular supplement users (n ¼ 97) received on average 207 mg folic acid per day from supplements. Conclusions: The folate status of Finnish adults seems to be adequate according to energy adjusted folate intake, plasma folate and homocysteine. The MTHFR homozygote frequency was low compared to other countries. Regular use of supplementary folic acid less than 300 mg increased plasma folate, but supplemental folic acid over 300 mg was required to lower tHcy values significantly.

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“…1 Hcy is metabolized by transsulfuration (depending on pyridoxine, vitamin B 6 ) and remethylation (depending on folic acid, vitamin B 9 and cobalamin, vitamin B 12 ) pathways. 2 In normal conditions, plasma content of Hcy varies from 3 to 15 mmol/L and higher plasma levels are considered as hyperhomocysteinemia (HHcy). There are three levels of HHcy: mild (15 to 30 mmol/L), moderate (30 to 100 mmol/L), and severe (4100 mmol/L).…”

Section: Introductionmentioning

confidence: 99%

Ablation of MMP9 Gene Ameliorates Paracellular Permeability and Fibrinogen–Amyloid Beta Complex Formation during Hyperhomocysteinemia

Muradashvili

Tyagi

Metreveli

et al. 2014

J Cereb Blood Flow Metab

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Increased blood level of homocysteine (Hcy), called hyperhomocysteinemia (HHcy) accompanies many cognitive disorders including Alzheimer's disease. We hypothesized that HHcy-enhanced cerebrovascular permeability occurs via activation of matrix metalloproteinase-9 (MMP9) and leads to an increased formation of fibrinogen-b-amyloid (Fg-Ab) complex. Cerebrovascular permeability changes were assessed in C57BL/6J (wild type, WT), cystathionine-b-synthase heterozygote (Cbs þ / À , a genetic model of HHcy), MMP9 gene knockout (Mmp9 À / À ), and Cbs and Mmp9 double knockout (Cbs þ / À /Mmp9 À / À ) mice using a dual-tracer probing method. Expression of vascular endothelial cadherin (VE-cadherin) and Fg-Ab complex formation was assessed in mouse brain cryosections by immunohistochemistry. Short-term memory of mice was assessed with a novel object recognition test. The cerebrovascular permeability in Cbs þ / À mice was increased via mainly the paracellular transport pathway. VE-cadherin expression was the lowest and Fg-Ab complex formation was the highest along with the diminished short-term memory in Cbs þ / À mice. These effects of HHcy were ameliorated in Cbs þ / À /Mmp9 À / À mice. Thus, HHcy causes activation of MMP9 increasing cerebrovascular permeability by downregulation of VE-cadherin resulting in an enhanced formation of Fg-Ab complex that can be associated with loss of memory. These data may lead to the identification of new targets for therapeutic intervention that can modulate HHcy-induced cerebrovascular permeability and resultant pathologies.

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Hyperhomocyst(e)inemia Is a Risk Factor for Arterial Endothelial Dysfunction in Humans

Cited by 141 publications

References 2 publications

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003–2004)

Plasma homocysteine concentration and blood pressure in healthy Iranian adults: the Tehran Homocysteine Survey (2003–2004)

Folate intake, plasma folate and homocysteine status in a random Finnish population

Ablation of MMP9 Gene Ameliorates Paracellular Permeability and Fibrinogen–Amyloid Beta Complex Formation during Hyperhomocysteinemia

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