Cardiovascular disease is a major cause of morbidity in aging and in HIV-infected individuals despite efficacy of cART, and furthermore, is associated with macrophage activation and inflammation. Nonhuman primates simulate human disease, and we previously reported that distinct macrophage populations play different roles in the pathogenesis of disease during SIV infection in rhesus macaques. For example, in the lung, short-lived macrophages were more readily destroyed by SIV and contributed to AIDS pathogenesis. Long-lived alveolar macrophages on the other hand were not easily destroyed by virus and thus may contribute to a long-term virus reservoir that also promotes chronic inflammation. The present studies extend this work to characterize macrophages in heart and skeletal muscles affecting cardiomyopathy observed during SIV/HIV infection as well as in heart tissues of uninfected younger and older macaques. The results demonstrated that macrophages are distributed uniformly throughout the heart tissues in animals of all age groups. Increased percentages of macrophages, however, were observed in hearts of aged macaques with similar increased percentages of macrophages in SIV-infected younger adult macaques. Interestingly, the increased macrophages of both aged uninfected and younger SIV-infected macaques was not due to increases in the absolute numbers of macrophages but rather to decreased heart muscle cellularity. This suggested that cardiovascular disease observed in aged as well as HIV-infected individuals may be due to similar mechanisms of decreased number of heart muscle cells and dysfunctional inflammatory long-lived macrophages of the heart.

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.