Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1096/fj.01-0196com | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
TLR4 Inhibition Attenuated LPS-Induced Proinflammatory Signaling and Cytokine Release in Mouse Hearts and Cardiomyocytes.
Immun Inflamm Dis
January 2025
Division of Physiology, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Background: Sepsis is associated with myocardial injury and early mortality. The innate immune receptor Toll-like receptor 4 (TLR4) can recognize pathogen-associated-molecular-patterns (PAMPs) and damage-associated molecular patterns (DAMPs); the latter are released during tissue injury. We hypothesized that TLR4 inhibition reduces proinflammatory signaling and cytokine release in: (1) LPS or Escherichia coli-treated isolated mouse heart; (2) LPS-treated mouse primary adult cardiomyocytes; and (3) the isolated heart during ischemia-reperfusion.
View Article and Find Full Text PDFACSL1 Aggravates Thromboinflammation by LPC/LPA Metabolic Axis in Hyperlipidemia Associated Myocardial Ischemia-Reperfusion Injury.
Adv Sci (Weinh)
January 2025
Shanghai Key Laboratory of Vascular Lesions and Remodeling, Department of Vascular Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
Acute myocardial infarction (AMI) is associated with well-established metabolic risk factors, especially hyperlipidemia and obesity. Myocardial ischemia-reperfusion injury (mIRI) significantly offsets the therapeutic efficacy of revascularization. Previous studies indicated that disrupted lipid homeostasis can lead to lipid peroxidation damage and inflammation, yet the underlying mechanisms remain unclear.
View Article and Find Full Text PDFNotoginsenoside R1 Attenuates H/R Injury in H9c2 Cells by Maintaining Mitochondrial Homeostasis.
Curr Issues Mol Biol
January 2025
School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia-reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear.
View Article and Find Full Text PDFAntiedemic Effect of the Myosin Light Chain Kinase Inhibitor PIK7 in the Rat Model of Myocardial Ischemia Reperfusion Injury.
Curr Issues Mol Biol
January 2025
Institute of Experimental Medicine, Almazov National Medical Research Centre, 15B Parkhomenko Street, 194021 Saint Petersburg, Russia.
Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase (MLCK)-dependent endothelial hyperpermeability, which is considered a preventable cause of reperfusion injury. In the present study, a single intravenous injection of MLCK peptide inhibitor PIK7 (2.
View Article and Find Full Text PDFThermosensitive Porcine Myocardial Extracellular Matrix Hydrogel Coupled with Proanthocyanidins for Cardiac Tissue Engineering.
Gels
January 2025
Laboratory of Immunotherapy and Tissue Engineering, Department of Cellular and Tissue Biology, Faculty of Medicine, National Autonomous University of Mexico, Av. Universidad 3000, Copilco Universidad, Coyoacán, Ciudad de México 04510, Mexico.
Currently, there are no therapies that prevent the negative myocardial remodeling process that occurs after a heart attack. Injectable hydrogels are a treatment option because they may replace the damaged extracellular matrix and, in addition, can be administered minimally invasively. Reactive oxygen species generated by ischemia-reperfusion damage can limit the therapeutic efficacy of injectable hydrogels.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!