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Endothelial Function: A Critical Determinant in Atherosclerosis?
Abstract
Common conditions predisposing to atherosclerosis, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with endothelial dysfunction. Endothelial function has largely been assessed as endothelium-dependent vasomotion, at least in part based on the assumption that impaired endothelium-dependent vasodilation also reflects the alteration of other important functions of the endothelium. An important rationale for this approach has been the observation that endothelium-derived nitric oxide (NO), a major mediator of endothelium-dependent vasodilation, has important anti-inflammatory and antithrombotic properties, ie, inhibiting leukocyte adhesion, limiting platelet adhesion and aggregation, and the expression of plasminogen activator inhibitor-1 (PAI-1), a prothrombotic protein. Accumulating data suggest that the degree of impairment of endothelium-dependent vasomotion has profound and independent prognostic implications. A common mechanism underlying endothelial dysfunction relates to increased vascular production of reactive oxygen species. Recent studies also suggest that inflammation per se and C-reactive protein in particular may directly contribute to endothelial dysfunction. These findings raise the question of whether assessment of endothelial function can be used in the clinical setting to identify patients at high risk. New insights into mechanisms of endothelial dysfunction, such as a better understanding of the regulation of important vascular sources of oxygen radicals, may lead to novel therapeutic strategies with the potential to improve prognosis.
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“It is noteworthy that all the studied parameters-endothelial dysfunction, 49 NT, 50 C-reactive protein, 51 IL-6, 51 and ICAM-1 51 -have been shown to be independent predictors of CVD.”
In the citing paper
“endothelial dysfunction, which can be defined as a reduced vasodilator response to acetylcholine, is an early prognostic indicator for the onset of cardiovascular disease (168–171).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [170]
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Metadata
- Authors
- Landmesser, U., Hornig, B., & Drexler, H.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- ORCID
- Landmesser, Ulf
- Venue
- Circulation
- Published
- 2004-06
- Volume
- 109
- Issue
- 21_suppl_1
- Pages
- II27-33
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2163221788
- Cited by
- 851
- References
- 78
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 10 · 2023: 16 · 2022: 11 · 2021: 29 · 2020: 27 · 2019: 20 · 2018: 38 · 2017: 42 · 2016: 47 · 2015: 44 · 2014: 47 · 2013: 59 · 2012: 42
- FWCI
- 35.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- endothelial dysfunction, endothelial function, atherosclerosis, endothelium-dependent vasodilation, nitric oxide, reactive oxygen species, inflammation, C-reactive protein, plasminogen activator inhibitor-1, hypertension, hypercholesterolemia, diabetes mellitus, smoking, cardiovascular risk prediction
- MeSH terms
- Animals, Arteriosclerosis, Endothelium, Vascular, Humans, Inflammation, Models, Cardiovascular, Nitric Oxide, Prognosis, Thrombosis, Reactive Oxygen Species, Mice
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