Similar cardiovascular disease histopathology and macrophages in heart tissues of younger adult SIV-infected and uninfected aged rhesus macaques

Abstract

Abstract 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.