Modulation of leukocyte–endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease
Abstract
Ischemia and reperfusion (I/R) are thought to play an important role in the pathophysiology of ischemic diseases of the heart. It is now well appreciated that leukocyte-endothelial cell interactions are important determinants for I/R-induced microvascular injury and dysfunction. There is a growing body of experimental data to suggest that reactive metabolites of oxygen and nitrogen are important physiological modulators of leukocyte-endothelial cell interactions. A number of investigators have demonstrated that I/R enhances oxidant production within the microcirculation resulting in increases in leukocyte adhesion and transendothelial cell migration. Several other studies have shown that exogenous nitric oxide (NO) donors may attenuate leukocyte and platelet adhesion and/or aggregation in a number of different inflammatory conditions including I/R. The objective of this review is to discuss the physiological chemistry of reactive metabolites of oxygen and nitrogen with special attention given to those interactions that may modulate leukocyte-endothelial cell interactions, provide an overview of the evidence implicating reactive metabolites of oxygen and nitrogen as modulators of leukocyte-endothelial cell interactions in vivo, and discuss how these mechanisms may be involved in the pathophysiology of ischemic heart disease.
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Decreased NO levels contribute to endothelial cell dysfunction, atherosclerotic plaque development, arteriosclerosis, vessel restenosis, peripheral vascular disease, and ischemia-reperfusion injury.
“It is well accepted that decreased NO levels contribute to endothelial cell dysfunction, atherosclerotic plaque development, arteriosclerosis, vessel restenosis, peripheral vascular disease, and ischemia-reperfusion injury [14, 15, 138–140].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [140]
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Self-citation
- Authors
- Grisham, M. B., Granger, D. N., & Lefer, D. J.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Grisham, Matthew B.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 1998-09
- Volume
- 25
- Issue
- 4-5
- Pages
- 404-433
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2094525668
- Cited by
- 293
- References
- 211
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 4 · 2020: 11 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 7 · 2013: 6 · 2012: 11
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk047663-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01 DK-43785, DK-47663, P01DK043785)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- reactive oxygen species, reactive nitrogen species, leukocyte-endothelium interaction, ischemia-reperfusion injury, ischemic heart disease, nitric oxide donors, leukocyte adhesion, transendothelial migration, platelet aggregation, microvascular damage, oxidative stress
- MeSH terms
- Animals, Cell Adhesion, Endothelium, Vascular, Humans, Iron, Leukocytes, Nitric Oxide, Oxidation-Reduction, Myocardial Reperfusion Injury, Myocardial Ischemia, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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