Chronic administration of mitochondrion-targeted peptide SS-31 prevents atherosclerotic development in ApoE knockout mice fed Western diet
Open accessAbstract
BACKGROUND: Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo. METHODS: Male ApoE-/- mice (8 weeks old) fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d) through subcutaneous injection for 12 weeks. Oil Red O staining was performed to evaluate area and sizes of the plaques. DHE staining and immunohistochemical staining of 8-OHDG was performed to assess the oxidative stress. The aorta ATP contents were assessed by the ATP bioluminescence assay kit. Immunohistochemical staining of CD68 and α-SMA and Masson's trichrome staining were performed to evaluate the composition of atherosclerotic plaque. Biochemical assays were performed to determine the protein level and activity of superoxide dismutase (SOD). The levels of CD36, LOX-1 and ABCA1 were immunohistochemically and biochemically determined to evaluate the cholesterol transport in aorta and peritoneal macrophages. Inflammatory factors, including ICAM-1, MCP-1, IL-6 and CRP in serum, were detected through ELISA. RESULTS: SS-31 administration reduced the area and sizes of western diet-induced atherosclerotic plaques and changed the composition of the plaques in ApoE-/- mice. Oxidative stress was suppressed, as evidenced by the reduced DHE stain, down-regulated 8-OHDG expression, and increased SOD activity after chronic SS-31 administration. Moreover, systemic inflammation was ameliorated as seen by decreasing serum ICAM-1, MCP-1, and IL-6 levels. Most importantly, SS-31 administration inhibited cholesterol influx by down-regulating expression of CD36 and LOX-1 to prevent lipid accumulation to further suppress the foam cell formation and atherosclerotic progression. CONCLUSION: Administration of SS-31 prevents against atherosclerotic formation in ApoE-/- mice suggesting that SS-31 might be considered to be a potential drug to prevent atherosclerotic progression.
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- Authors
- Zhang, M., Zhao, H., Cai, J., Li, H., Wu, Q., Qiao, T., & Li, K.
- Affiliations
- Nanjing Drum Tower Hospital (CN)
- Nanjing University (CN)
- Corresponding author
- Qiao, Tong
- Li, Kuanyu
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-09-29
- Volume
- 12
- Issue
- 9
- Pages
- e0185688
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5621700
- OpenAlex
- W2757694213
- Cited by
- 45
- References
- 37
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- The National Basic Research Program of China (“973” program) (2015CB856300)
- The National Natural Science Foundation of China (31571218, 81370387)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- SS-31, atherosclerosis, ApoE-deficient mice, Western diet, oxidative stress, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine, inflammation, foam cell formation, cholesterol absorption, CD36, LOX-1, ABCA1, atherosclerotic plaque composition, mitochondrial cardiolipin
- MeSH terms
- Adenosine Triphosphate, Animals, Apolipoproteins E, Cells, Cultured, Male, Mice, Inbred C57BL, Mitochondria, Oligopeptides, Mice, Knockout, Oxidative Stress, Atherosclerosis, Mice, Diet, Western
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