Anna Babinska1, Cristina C Clement2, Tomasz Przygodzki3, Marcin Talar3, Yan Li4, Marcin Braun5, Joanna Wzorek3, Maria Swiatkowska6, Yigal H Ehrlich7, Elizabeth Kornecki8, Cezary Watala3, Moro O Salifu9. 1. Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA. Electronic address: anna.babinska@downstate.edu. 2. Department of Pathology, Albert Einstein College of Medicine, New York, 10461, USA; Department of Chemistry, Lehman College, CUNY, Bronx, New York 10468, USA. 3. Department of Haemostasis and Haemostatic Disorders, Biomedical Sciences, Medical University of Lodz, 92-215, Lodz, Poland. 4. Department of Neurology, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA. 5. Department of Pathology, Medical Univeristy of Lodz, 92-213, Lodz, Poland. 6. Department of Cytobiology and Proteomics, Biomedical Sciences, Medical University of Lodz, 92-215, Lodz, Poland. 7. Program in Neuroscience, College of Staten Island of the City University of New York, Staten Island, NY, 10314, USA. 8. Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA; Department of Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA. 9. Department of Medicine, State University of New York, Downstate Medical Center, Brooklyn, NY, 11203, USA.
Abstract
BACKGROUND AND AIMS: The F11 Receptor (F11R), AKA Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is an adhesion protein constitutively expressed on the membrane surface of circulating platelets and the luminal surface of inflamed endothelial cells (EC). Platelet adhesion to an inflamed endothelium is one of the early steps of atherosclerotic plaque formation. Our previous studies, conducted with cultured EC in vitro, have demonstrated the expression of F11R/JAM-A on the luminal surface of inflamed EC, platelet adhesion to inflamed EC through F11R/JAM-A interactions, and inhibition of this interaction by the presence of F11R/JAM-A antagonistic peptide (F11Rpeptide 4D). In the present study, we examined in vivo the overall health-benefits and cardiovascular effects of long-term treatment of animals prone to atherosclerosis, ApoE-/- mice, with F11R-peptide 4D. METHODS: Twenty ApoE-/- mice were assigned to daily treatment with peptide 4D and compared to their counterparts control untreated mice. Mice were observed for wellness and survival. Plaque size in the aorta and heart was measured using histological analysis. Effects of peptide 4D (or scramble control) on platelet adhesion to inflamed endothelium were measured using intravital microscopy. RESULTS: Significant reductions in atherosclerotic plaques number and size, an overall robust health with longer survival were found in the peptide 4D treated group of ApoE-/- mice. Intravital microscopic studies conducted in exposed vessels of ApoE-/- mice demonstrated significant inhibition by peptide 4D of platelet adhesion to the cytokine-inflamed endothelium. CONCLUSIONS: Our results demonstrate that peptide 4D significantly reduces atherosclerotic plaque formation in ApoE-/- mice and inhibits platelet adhesion to the inflamed arterial endothelium.
BACKGROUND AND AIMS: The F11 Receptor (F11R), AKA Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is an adhesion protein constitutively expressed on the membrane surface of circulating platelets and the luminal surface of inflamed endothelial cells (EC). Platelet adhesion to an inflamed endothelium is one of the early steps of atherosclerotic plaque formation. Our previous studies, conducted with cultured EC in vitro, have demonstrated the expression of F11R/JAM-A on the luminal surface of inflamed EC, platelet adhesion to inflamed EC through F11R/JAM-A interactions, and inhibition of this interaction by the presence of F11R/JAM-A antagonistic peptide (F11Rpeptide 4D). In the present study, we examined in vivo the overall health-benefits and cardiovascular effects of long-term treatment of animals prone to atherosclerosis, ApoE-/- mice, with F11R-peptide 4D. METHODS: Twenty ApoE-/- mice were assigned to daily treatment with peptide 4D and compared to their counterparts control untreated mice. Mice were observed for wellness and survival. Plaque size in the aorta and heart was measured using histological analysis. Effects of peptide 4D (or scramble control) on platelet adhesion to inflamed endothelium were measured using intravital microscopy. RESULTS: Significant reductions in atherosclerotic plaques number and size, an overall robust health with longer survival were found in the peptide 4D treated group of ApoE-/- mice. Intravital microscopic studies conducted in exposed vessels of ApoE-/- mice demonstrated significant inhibition by peptide 4D of platelet adhesion to the cytokine-inflamed endothelium. CONCLUSIONS: Our results demonstrate that peptide 4D significantly reduces atherosclerotic plaque formation in ApoE-/- mice and inhibits platelet adhesion to the inflamed arterial endothelium.
Authors: Dominik Rath; Vera Rapp; Jessica Schwartz; Stefan Winter; Frederic Emschermann; Daniel Arnold; Johannes Rheinlaender; Manuela Büttcher; Michael Strebl; Michael B Braun; Konstanze Altgelt; Álvaro Petersen Uribe; Christoph Schories; Denis Canjuga; Elke Schaeffeler; Oliver Borst; Tilman E Schäffer; Harald Langer; Thilo Stehle; Matthias Schwab; Tobias Geisler; Meinrad Gawaz; Madhumita Chatterjee Journal: JACC Basic Transl Sci Date: 2022-05-23
Authors: Jun Chen; Xixi Zhang; Reid Millican; Jennifer Sherwood; Sean Martin; Hanjoong Jo; Young-Sup Yoon; Brigitta C Brott; Ho-Wook Jun Journal: Adv Drug Deliv Rev Date: 2021-01-09 Impact factor: 15.470
Authors: Radoslaw Bednarek; Anna Selmi; Dagmara Wojkowska; Kamil Karolczak; Marcin Popielarski; Marta Stasiak; Moro O Salifu; Anna Babinska; Maria Swiatkowska Journal: Breast Cancer Res Treat Date: 2019-10-24 Impact factor: 4.872