Cited by 144Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyNeuroprotection in Cerebral Ischemia

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Potent mitochondria-targeted peptides reduce myocardial infarction in rats

Cho, Janghyun, Won, Kyungheon, Wu, DunLi, Soong, Yi, Liu, Shaoyi, Szeto, Hazel H., Hong, Mun K.·2007·Coronary Artery Disease

DOI 10.1097/01.mca.0000236285.71683.b6

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Abstract

OBJECTIVE: Previously, we demonstrated that a novel opiate peptide, 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2, provided cardioprotection against myocardial stunning in vivo. We subsequently showed that this peptide targeted mitochondria and can scavenge reactive oxygen species. The objective of this study was to determine the role of opioid versus antioxidant activity in cardioprotection. METHODS: We compared two mitochondria-targeted peptide analogs that lacked opioid activity: SS-31 (D-Arg-2',6'-dimethyl-tyrosine-Lys-Phe-NH2) and SS-20 (Phe-D-Arg-Phe-Lys-NH2). They differ in that only SS-31 has scavenging ability. Rats (n=8/group) were randomized to SS-31, SS-20 or placebo. The drugs (3 mg/kg) or saline was administered intraperitoneally 30 min before ligation of the left anterior descending artery for 60 min, and another dose given intraperitoneally 5 min before reperfusion for 60 min. Study endpoints included myocardial infarct size, cardiac arrhythmia and myocardial lipid peroxidation. RESULTS: The area at risk was similar among the groups. The infarct area/area at risk, however, was significantly smaller in the treatment groups (53.9+/-1.1% in SS-31 group, 47.1+/-1.4% in SS-20 group, versus 59.9+/-1% in the controls, P<0.01). Lipid peroxidation was significantly reduced by both SS-31 and SS-20 treatment. Arrhythmia occurred only during the early period of coronary occlusion and was less frequent and less severe in the peptide treatment groups than in the controls (Lambeth score 5 points, 3 points, versus 13 points in the controls, P<0.05). CONCLUSIONS: This study shows that pretreatment with both SS-31 and SS-20 significantly reduced myocardial lipid peroxidation and infarct size in ischemia-reperfusion injury, and suggests that the cardioprotective properties of 2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it most likely reduces reactive oxygen species production during ischemia-reperfusion.

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Authors: Cho, J., Won, K., Wu, D., Soong, Y., Liu, S., Szeto, H. H., & Hong, M. K.
Affiliations: Cornell University (US)
Weill Cornell Medicine (US)
St. Luke's-Roosevelt Hospital Center (US)
Corresponding author: Cho, Janghyun
Szeto, Hazel H.
Hong, Mun K.
ORCID: Liu, Shaoyi
Szeto, Hazel H.
Venue: Coronary Artery Disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2007-05
Volume: 18
Issue: 3
Pages: 215-220
ISSN: 0954-6928 (ISSN-L)
DOI: 10.1097/01.mca.0000236285.71683.b6
OpenAlex: W2003139013
Cited by: 144
References: 18
Citations by year: 2026: 5 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 12 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 15 · 2012: 14
FWCI: 3.07
Type: journal article
Language: en
Open access: closed
Locations: Coronary Artery Disease (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Drug Abuse (P01 DA 08924, P01DA008924)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords: SS-31, mitochondria-targeted peptide, myocardial infarction, cardioprotection, ischemia-reperfusion injury, reactive oxygen species scavenging, lipid peroxidation, cardiac arrhythmias, opioid peptides, myocardial stunning
MeSH terms: Animals, Antioxidants, Male, Mitochondria, Myocardial Infarction, Oligopeptides, Lipid Peroxidation, Myocardial Reperfusion, Rats, Sprague-Dawley, Reactive Oxygen Species, Rats

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Potent mitochondria-targeted peptides reduce myocardial infarction in rats

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