Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model
Open accessAbstract
Although hyperhomocysteinemia (HHcy) is a well-known risk factor for the development of cardiovascular disease, the underlying molecular mechanisms are not fully elucidated. Here we show that induction of HHcy in apoE-null mice by a diet enriched in methionine but depleted in folate and vitamins B6 and B12 increased atherosclerotic lesion area and complexity, and enhanced expression of receptor for advanced glycation end products (RAGE), VCAM-1, tissue factor, and MMP-9 in the vasculature. These homocysteine-mediated (HC-mediated) effects were significantly suppressed, in parallel with decreased levels of plasma HC, upon dietary supplementation with folate and vitamins B6/B12. These findings implicate HHcy in atherosclerotic plaque progression and stability, and they suggest that dietary enrichment in vitamins essential for the metabolism of HC may impart protective effects in the vasculature.
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Hyperhomocysteinemia can induce vascular endothelial injury and is one of the main risk factors for cardiovascular diseases.
“Hyperhomocysteinemia (HHcy) can induces vascular endothelial injury, and has been determined to be one of the main risk factors for cardiovascular diseases,2, 3”
From Picroside <scp>II</scp> attenuates hyperhomocysteinemia‐induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis (2019) · cites this paper as [3]
The Introduction reports that elevated homocysteine is associated with increased cardiovascular risk and may cause oxidative damage at the vascular interface; it also describes impaired endothelial-dependent vasodilation in people with experimentally induced hyperhomocysteinemia. This supports the endothelial-injury point, but the paper does not establish that hyperhomocysteinemia is *one of the main* cardiovascular risk factors. (LLM, conf=0.85)
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Research works printed but not linked: 3
- Eikelboom, J.W., Lonn, E., Genest, J., Jr., Hankey, G., and Yusuf, S. 1999. Homocyst(e)ine and cardiovascular disease: a critical review of the epi- demiologic evidence. Ann. Intern. Med. 131:363-375.
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- Authors
- Hofmann, M. A., Lalla, E., Lu, Y., Gleason, M. R., Wolf, B. M., Tanji, N., Ferran, L. J., Kohl, B., Rao, V., Kisiel, W., Stern, D. M., & Schmidt, A. M.
- Affiliations
- Columbia University (US)
- Heidelberg University (DE)
- The University of Texas Health Science Center at Tyler (US)
- University of New Mexico (US)
- Corresponding author
- Hofmann, Marion A.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-03-15
- Volume
- 107
- Issue
- 6
- Pages
- 675-683
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC208940
- OpenAlex
- W2116164680
- Cited by
- 529
- References
- 1
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 11 · 2023: 8 · 2022: 15 · 2021: 15 · 2020: 17 · 2019: 6 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 18 · 2014: 27 · 2013: 18 · 2012: 25
- FWCI
- 23.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- American Heart Association
- U.S. Public Health Service
- Topics
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- hyperhomocysteinemia, atherosclerosis, vascular inflammation, receptor for advanced glycation end products, VCAM-1, tissue factor, MMP-9, folic acid supplementation, vitamin B6, vitamin B12, ApoE-null mice, atherosclerotic plaque stability, cardiovascular risk factors
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Apolipoproteins E, Arteriosclerosis, Cells, Cultured, Diet, Disease Models, Animal, Folic Acid, Humans, Immunohistochemistry, Male, Methionine, Mice, Inbred C57BL, Pyridoxine, Receptors, Immunologic, Thromboplastin, Vasculitis, Vitamin B 12, Mice, Knockout, Vascular Cell Adhesion Molecule-1, Hyperhomocysteinemia, Matrix Metalloproteinase 9, Mice
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