Related Experiment Videos
Homocysteine and vascular dysfunction
1Veterans Affairs Medical Center, Iowa City, IA 52246, USA. steven-lentz@uiowa.edu
Insights
Elevated homocysteine (homocyst(e)ine) levels are linked to vascular disease risk. Research suggests homocysteine may directly harm blood vessels, potentially through oxidative stress, but more studies are needed.
Area of Science:
- Cardiovascular Science
- Biochemistry
- Vascular Biology
Background:
- Elevated plasma homocysteine (homocyst(e)ine) is associated with increased risk of thrombotic and atherosclerotic vascular disease.
- The causal role of homocyst(e)ine versus associated conditions in vascular disease remains unclear.
- Dietary interventions to lower homocyst(e)ine are proposed for vascular disease prevention.
Purpose of the Study:
- To investigate whether elevated plasma homocyst(e)ine concentration directly causes vascular disease.
- To explore the mechanisms by which homocysteine may contribute to vascular dysfunction.
- To evaluate the role of homocysteine-induced oxidant stress in endothelial dysfunction.
Main Methods:
- Review of in vitro cell studies, animal models, and human studies on hyperhomocyst(e)inemia.
- Analysis of findings related to endothelial phenotype alteration and reactive oxygen species generation.
- Examination of evidence supporting homocysteine's role in atherosclerosis, thrombosis, and vasospasm.
Main Results:
- In vitro studies suggest homocysteine may alter endothelial cell function, potentially via peroxide generation.
- Animal and human models of hyperhomocyst(e)inemia show support for the hypothesis of homocysteine-induced endothelial dysfunction.
- Endothelial dysfunction in hyperhomocyst(e)inemia may contribute to atherosclerosis and complications like thrombosis and vasospasm.
Conclusions:
- Homocysteine may directly contribute to vascular dysfunction and disease development.
- Homocysteine-induced oxidant stress is a potential mechanism underlying endothelial dysfunction.
- Future research should clarify the role of homocysteine versus associated conditions (e.g., folate deficiency) and the benefits of B vitamin supplementation.
Abstract:
Elevated plasma levels of homocysteine and disulfide adducts of homocysteine (collectively termed "homocyst(e)ine") are associated with increased risk of thrombotic and atherosclerotic vascular disease. It is still not evident, however, whether moderately elevated plasma homocyst(e)ine concentration per se is a cause, or rather just a marker for an associated condition that may predispose to development of vascular disease or its complications. This distinction has important clinical consequences, since dietary intervention to lower plasma homocyst(e)ine has been proposed as a global strategy to decrease the prevalence of vascular disease. Studies of cultured cells in vitro have led to the hypothesis that homocysteine may predispose to vascular disease by altering the normally antithrombotic and vasoprotective phenotype of vascular endothelium, perhaps through a mechanism that involves generation of peroxides and other reactive oxygen species. Recent findings in animal and human models of moderate hyperhomocyst(e)inemia provide support for some aspects of this hypothesis. Endothelial dysfunction in hyperhomocyst(e)inemia may contribute to development of atherosclerosis and predispose to complications such as thrombosis and vasospasm. Important questions to be addressed in future investigations include the relative importance of homocysteine versus associated conditions (such as folate deficiency) in the etiology of vascular dysfunction, the role of homocysteine-induced oxidant stress, and the potential benefits of lowering plasma homocyst(e)ine levels through dietary supplementation with B vitamins.