title: Selective subepicardial localization of monocyte subsets in response to progressive coronary artery constriction.
abstract: Following myocardial infarction and atherosclerotic lesion development, monocytes contribute to myocardial protection and repair, while also partaking in myocardial ischemic injury. The balance of proinflammatory and reparative monocyte subsets is crucial in governing these therapeutic and pathological outcomes. Myocardial ischemic damage displays heterogeneity across the myocardium, whereby the subendocardium shows greatest vulnerability to ischemic damage. In this study we examined the transmural distribution of monocyte subsets in response to gradual coronary artery occlusion. CD14(+) monocytes were isolated from peripheral blood of New Zealand White rabbits and divided into two subgroups based on the expression of CD62L. We employed a rabbit model of progressive coronary artery obstruction to induce chronic myocardial ischemia and reinfused fluorescently labeled autologous monocytes. The distribution of fluorescently labeled autologous monocytes was examined with a high-resolution three-dimensional imaging cryomicrotome. The subepicardial layer contained the largest infiltration of both monocyte subgroups, with a significantly greater proportion of CD14(+)CD62L(+) monocytes at the time when the ischemic area was at a maximum. By targeting CD13(+) angiogenic vessels, we confirmed the presence of angiogenesis in epicardial and midmyocardial regions. These myocardial regions demonstrated the highest level of infiltration of both monocyte subsets. Furthermore, CD14(+)CD62L(+) monocytes showed significantly greater migration towards monocyte chemoattractant protein-1, greater adhesive capacity, and higher expression of C-C chemokine receptor type-2 relative to CD14(+)CD62L(-) monocytes. In conclusion, we note selective subepicardial distribution of monocyte subpopulations, with changes in proportion depending on the time after onset of coronary narrowing. Selective homing is supported by divergent migratory properties of each respective monocyte subgroup.
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Nazanin
authors.initials: N
authors.lastname: Hakimzadeh
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Monique G J T B
authors.initials: MG
authors.lastname: van Lier
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Pepijn
authors.initials: P
authors.lastname: van Horssen
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Mariah
authors.initials: M
authors.lastname: Daal
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Duy Ha
authors.initials: DH
authors.lastname: Ly
authors.affiliation: Deptartment of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and.
authors.forename: Charly
authors.initials: C
authors.lastname: Belterman
authors.affiliation: Deptartment of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and IHU Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.
authors.forename: Ruben
authors.initials: R
authors.lastname: Coronel
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Jos A E
authors.initials: JA
authors.lastname: Spaan
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; m.siebes@amc.uva.nl.
authors.forename: Maria
authors.identifier: 0000-0002-7034-5843
authors.initials: M
authors.lastname: Siebes
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D018826:CD13 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003250:Constriction; D023921:Coronary Stenosis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D019041:L-Selectin / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018919:Neovascularization, Physiologic; D010641:Phenotype; D011817:Rabbits; D012038:Regeneration; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018950:Lipopolysaccharide Receptors; D019041:L-Selectin; D018826:CD13 Antigens
keywords: cellular imaging; macrophages; monocytes; myocardial ischemia; neovascularization