Background: Antibody therapy to inhibit either P-selectin or intercellular adhesion molecule-1 (ICAM-1) has been reported to provide myocardial protection against leukocyte-mediated reperfusion injury. Because these molecules play different roles in the leukocyte-endothelial interaction, co-inhibition of both may achieve further enhanced cardioprotection. In addition, the therapeutic efficacy of such antibody therapy may be affected by the delivery route used. Retrograde intracoronary infusion will offer an effective, direct access to the postcapillary venules, where the target event (leukocyte-endothelial interaction) takes place. We investigated the feasibility and efficiency of the combined antibody therapy targeting both P-selection and ICAM-1 via the retrograde intracoronary route to attenuate myocardial ischemia-reperfusion injury.
Methods And Results: Lewis rats underwent 30-minute left coronary artery occlusion. Just before reperfusion, anti-P-selectin monoclonal antibody (150 microg/kg), anti-ICAM-1 monoclonal antibody (200 microg/kg), both antibodies together, or control antibody were retrogradely infused into the left cardiac vein. At 24 hours after reperfusion, administration of either anti-P-selectin or anti-ICAM-1 antibody significantly (P<0.05) improved left ventricular ejection fraction and attenuated infarct size (40.6+/-3.2% and 34.8+/-3.5%, respectively) compared with the control (56.8+/-3.4%). This was associated with reduced leukocyte accumulation and improved regional blood flow in the ischemic area. Noticeably, co-administration of both antibodies achieved a much greater reduction in infarct size (19.1+/-3.6%), associated with greater attenuation in leukocyte infiltration, compared with administration of either single antibody.
Conclusions: Combined antibody therapy inhibiting both P-selectin and ICAM-1 via the retrograde intracoronary route could be a promising new strategy for myocardial protection against ischemia-reperfusion injury.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1161/CIRCULATIONAHA.105.000794 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma anti-CD4 IgG levels are associated with poor immune recovery in people with HIV initiating antiretroviral therapy.
AIDS
February 2025
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY.
A segment of people with HIV on effective antiretroviral therapy (ART) continue to experience poor immune recovery, leaving them at heightened risk of non-AIDS-defining events (NAEs). The production of anti-CD4 IgG autoreactive antibodies is suggested as one contributing mechanism to these complications. Here, we found that plasma anti-CD4 levels do not discriminate immunological responders from nonresponders nor predict the occurrence of NAEs, suggesting it is unlikely a contributing immunopathological factor associated with these complications.
View Article and Find Full Text PDFIn Vitro Experiment Present ROCK2 Inhibition Promotes the Therapeutic of Bevacizumab in Treatment of Glioblastoma Multiforme.
Clin Neuropharmacol
October 2024
Department of Neurosurgery, Yubei District Hospital of TCM, Chongqing, China.
Objective: Gliomas are a general designation for neuroepithelial tumors derived from the glial cells of the central nervous system. According to the histopathological and immunohistochemical features, the World Health Organization classifies gliomas into four grades. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor that has been approved for the treatment of glioblastoma multiforme (GBM) as a second-line therapy.
View Article and Find Full Text PDFA signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells.
Proc Natl Acad Sci U S A
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.
View Article and Find Full Text PDFCryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.
Proc Natl Acad Sci U S A
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.
View Article and Find Full Text PDFChanges in serum periostin levels in uncontrolled asthma in children (DADO phase 2 study).
Allergol Immunopathol (Madr)
January 2025
Department of Biological Sciences, University of Extremadura, Spain.
Objective: Asthma is an inflammatory airway condition and the most common chronic disease in children. However, there is a lack of biological markers for asthma, especially in children. This study aimed to analyze the changes in periostin levels in children with uncontrolled asthma after 12 months of optimized management.
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!