Manganese superoxide dismutase polymorphism affects the oxidized low-density lipoprotein-induced apoptosis of macrophages and coronary artery disease
Abstract
AIMS: Oxidative damage promotes atherosclerosis. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme localized in mitochondria. We investigated the associations of the MnSOD polymorphism (valine-to-alanine in the mitochondrial-targeting domain) with its activity in leukocytes, with macrophage apoptosis by oxidized low-density lipoprotein (oxLDL), and with coronary artery disease (CAD). METHODS AND RESULTS: Blood samples were taken from 50 healthy subjects. The mitochondrial MnSOD activities in leukocytes were 542.4 +/- 71.6 U/mg protein (alanine/alanine, n = 2), 302.0 +/- 94.9 U/mg protein (alanine/valine, n = 12), and 134.0 +/- 67.1 U/mg protein (valine/valine, n = 36; P < 0.0001 for non-valine/valine vs. valine/valine). Macrophages were treated with oxLDL. After incubation, the percentages of apoptotic macrophages were 48.6 +/- 3.6% (alanine/alanine), 78.6 +/- 9.8% (alanine/valine), and 87.5 +/- 7.0% (valine/valine) (P < 0.0001, non-valine/valine vs. valine/valine). The association of the MnSOD polymorphism with CAD was investigated using blood samples collected from 498 CAD patients and 627 healthy subjects; the alanine allele was found to reduce the risk of CAD and acute myocardial infarction (AMI). CONCLUSION: Our data indicate that the alanine variant of signal peptide increases the mitochondrial MnSOD activity, protects macrophages against the oxLDL-induced apoptosis, and reduces the risk of CAD and AMI.
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Specific polymorphisms in the gene for MnSOD have been established as an independent risk factor for coronary artery disease.
“Notably, specific polymorphisms in the gene for MnSOD have been established as an independent risk factor for coronary artery disease (317).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [317]
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- Authors
- Fujimoto, H., Taguchi, J.-I., Imai, Y., Ayabe, S., Hashimoto, H., Kobayashi, H., Ogasawara, K., Aizawa, T., Yamakado, M., Nagai, R., & Ohno, M.
- Affiliations
- The University of Tokyo (JP)
- Cardiovascular Institute Hospital (JP)
- Mitsui Memorial Hospital (JP)
- Toranomon Hospital (JP)
- Corresponding author
- Ohno, Minoru
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-10-29
- Volume
- 29
- Issue
- 10
- Pages
- 1267-1274
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2136317945
- Cited by
- 84
- References
- 29
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 9 · 2014: 4 · 2013: 6 · 2012: 5
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- manganese superoxide dismutase, oxidized LDL, macrophage apoptosis, coronary artery disease, acute myocardial infarction, atherosclerosis, oxidative stress, mitochondrial antioxidant enzymes, signal peptide, genetic susceptibility
- MeSH terms
- Adult, Aged, Aged, 80 and over, Coronary Artery Disease, Female, Humans, Leukocytes, Lipoproteins, LDL, Macrophages, Male, Middle Aged, Myocardial Infarction, Polymorphism, Genetic, Superoxide Dismutase, Apoptosis
About these checks
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