A theory for the mechanism of homocysteine-induced vascular pathogenesis

Wang, Xiao

doi:10.1054/mehy.1998.0787

Cited by 14 publications

(8 citation statements)

References 57 publications

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“…Studies in adult baboons did show endothelium desquamation, but only after months of hyperhomocysteinemia. 7 Oxidative stress 29 and disruption of calcium-dependent cell adhesions/junctions 30 were proposed as mechanisms through which homocysteine damages the endothelium. However, the results from our studies reveal that the embryonic endothelium detachment cannot be explained by a general effect of homocysteine thiolactone only, because in that case we would expect all vessels to show endothelial detachment and a similar mor-phology of the pharyngeal arch arteries in the NT embryos and the CS embryos.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Induces Endothelial Cell Detachment and Vessel Wall Thickening During Chick Embryonic Development

Boot

Steegers‐Theunissen

Poelmann

et al. 2004

Circulation Research

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Homocysteine affects the migration and differentiation of neural crest cells in vitro and can result in neural tube defects in vivo. Furthermore, homocysteine has been described as an important determinant in vascular disease in human adults. However, little is known about the effects of homocysteine on the development of embryonic vessels. In this study, we injected homocysteine (30 micromol/L) into the neural tube lumen of chick embryos at the time point of neural crest cell emigration, and analyzed the effects on the neural crest-derived pharyngeal arch arteries, like the brachiocephalic arteries, and the mesoderm-derived arteries, such as the dorsal aorta. By stage HH35, we observed detachment of the endothelium, decreased expression of the extracellular matrix proteins fibrillin-2, and fibronectin in the pharyngeal arch arteries, whereas the dorsal aorta was identical in homocysteine-neural tube-injected and control embryos. No effect of homocysteine on endothelin-1 mRNA expression was observed. By stage HH40, the brachiocephalic arteries of homocysteine-neural tube-injected embryos displayed a decreased lumen diameter, an increased intima- and media-thickness, and an increased number of actin layers compared with the brachiocephalic arteries in control embryos. We propose that homocysteine affects the neural crest-derived smooth muscle cells and their extracellular matrix proteins in the pharyngeal arch arteries, resulting in an abnormal smooth muscle to endothelial cell interaction, leading to endothelial cell detachment. We suggest that, as in adult life, increased homocysteine concentrations lead to vascular damage in the embryo. This prenatal damage might increase the susceptibility to develop vessel pathology later in life.

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Section: Discussionmentioning

confidence: 99%

Homocysteine Induces Endothelial Cell Detachment and Vessel Wall Thickening During Chick Embryonic Development

Boot

Steegers‐Theunissen

Poelmann

et al. 2004

Circulation Research

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“…Elevated homocysteine concentrations are present in individuals who develop atherosclerotic vascular disease, coronary heart disease or peripheral vascular disease. The mechanism may be a direct angiotoxicity, involving endothelial and vascular smooth muscle cell injury and impaired thrombolysis (Wang 1999).…”

Section: Introductionmentioning

confidence: 99%

Prospective evaluation of a peripherally administered three‐in‐one parenteral nutrition product in dogs

Chandler

Payne-James

2006

J of Small Animal Practice

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“…This finding might explain the higher degree of CIT in Gp2 and Gp3 compared to Gp1 (young healthy controls). It is hypothesized that the high tHcy level induces procoagulative effects that result in endothelial damage 41 , 42 that could precipitate the rupture of an established atherosclerotic plaque 25 , 41 , 43 .…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma homocysteine is positively associated with age independent of C677T mutation of the methylenetetrahydrofolate reductase gene in selected Egyptian subjects

Elsammak¹,

Kandil²,

El-Hifni³

et al. 2004

Int. J. Med. Sci.

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This study aimed to evaluate the plasma homocysteine (tHcy) and folate levels as well as the methylenetetrahydrofolate reductase (MTHFR) C677T mutation in Egyptian subjects. Fasting total homocysteine (tHcy) and the (MTHFR) C677T mutation were evaluated in 50 healthy young control males (age 35-50 years, Gp1), 50 elderly males age ranged between 50-75 years without any cardiovascular diseases (Gp2) and 50 age matched elderly male patients (Gp3) with myocardial infarction. There was a significant elevation of plasma tHcy in the patients group and Gp2 compared to the young control group (Gp1). The total plasma homocysteine (tHcy) in the control group, Gp2 and the patients group were 17.99 ± 9.76, 39.9 ± 20.06 and 43.8 ± 13.13 μmol/L respectively. The frequency of the TT genotype was 12% in the patient group compared with 8 % in the young healthy controls and elderly subjects (Gp2). The CT genotype constituted 36%, 48% and 44% in the control group, Gp2 and the patients group respectively. There was no significant difference in the occurrence of the TT genotype between the studied groups. Plasma tHcy correlated positively with age, total cholesterol, urea, creatinine, glucose levels and carotid intimal thickness (CIT). Conclusion: The MTHFR mutation does not seem to be associated with either high tHcy or the occurrence of cardiovascular diseases in the studied patients. However, elevated plasma tHcy level positively correlates with age in the studied subjects.

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A theory for the mechanism of homocysteine-induced vascular pathogenesis

Cited by 14 publications

References 57 publications

Homocysteine Induces Endothelial Cell Detachment and Vessel Wall Thickening During Chick Embryonic Development

Homocysteine Induces Endothelial Cell Detachment and Vessel Wall Thickening During Chick Embryonic Development

Prospective evaluation of a peripherally administered three‐in‐one parenteral nutrition product in dogs

Elevated plasma homocysteine is positively associated with age independent of C677T mutation of the methylenetetrahydrofolate reductase gene in selected Egyptian subjects

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