Characterization of heart macrophages in rhesus macaques as a model to study cardiovascular disease in humans

Abstract

Rhesus macaques are physiologically similar to humans and, thus, have served as useful animal models of human diseases including cardiovascular disease. The purpose of this study was to characterize the distribution, composition, and phenotype of macrophages in heart tissues of very young (fetus: 0.5 years, n = 6), young adult (2-12 years, n = 12), and older adult (13-24 years, n = 9) rhesus macaques using histopathology and immunofluorescence microscopy. Results demonstrated that macrophages were uniformly distributed throughout the heart in animals of all age groups and were more prevalent than CD3-positve T-cells and CD20-positive B-cells.Macrophages comprised approximately 2% of heart tissue cells in the younger animals and increased to a mean of nearly 4% in the older adults. CD163-positive macrophages predominated over HAM56-positive and CD206-positive macrophages, and were detected at significantly higher percentage in the animals between 13 and 24 years of age, as well as in heart tissues exhibiting severe histopathology or inflammation in animals of all age groups. In vivo dextran labeling and retention indicated that approximately half of the macrophages were longer lived in healthy adult heart tissues and may comprise the tissue-resident population of macrophages.These results provide a basis for continued studies to examine the specific functional roles of macrophage subpopulations in heart tissues during homeostasis and in cardiovascular disease for then developing intervention strategies.

Activation of Immune System May Cause Pathophysiological Changes in the Myocardium of SARS-CoV-2 Infected Monkey Model

“…Despite ongoing research, the characterization of extra-pulmonary manifestation in organs such as the heart through histopathological means has been limited to endomyocardial biopsies and autopsy sections of deceased patients [ 20 , 21 , 23 , 24 , 25 , 26 , 27 , 28 ]. Nonhuman primates (NHPs) are physiologically similar to humans and serve as a valuable model to study cardiovascular disease [ 29 ]. To the best of our knowledge, COVID-19-associated myocardial injury in the monkey model has not been extensively explored.…”

Macrophages and HIV/AIDS Pathogenesis: Lessons from the Rhesus Macaque Model

“…d. Heart. In an early study characterizing heart tissues of rhesus macaques, macrophages were uniformly distributed throughout the heart in animals of all age groups ranging from infants to elderly adults, and were more prevalent than CD3 + T cells and CD20 + B cells [32]. Macrophages comprised approximately 2% of heart tissue cells in the younger animals and increased to a mean of nearly 4% in the older adults.…”

“…To detect longer-lived macrophages, dextran, a branched polymer of anhydroglucose can be administered. Phagocytic cells take up fluorescein-labeled dextran, and long-lived macrophages containing the conjugated dextran can be identified weeks or months later whereas the shorter-lived cells with dextran die in a few days and are replaced with recently-recruited unlabeled cells [22,32].…”

Development of a Geropathology Grading Platform for nonhuman primates

“…Therefore, nonhuman primates (NHPs) are considered an excellent translational model as they share many similarities in aging and spontaneous chronic diseases with humans [3,9]. For example, the interactive nature of cognitive aging, synaptic aging, and endocrine status has been described in NHPs [10], and a relationship between increasing tissue macrophages in heart during aging has been identified [11]. However, there are very few detailed analyses of NHP peripheral organs on how systemic pathologic alterations may be associated with neuronal changes.…”