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.