A Small Animal Model to Study Cardiac Fibrosis in Chronic HIV Infection

The effect of HIV on the heart is complex and continues throughout the lifetime of the individual. Without antiviral treatment opportunistic infections can cause serious damage. With antivirals the effect of opportunistic infection is mitigated. However, the continued existence of viable HIV in the reservoirs creates a state of persistent inflammation which contributes to cardiac abnormalities. Typically, inflammatory monocytes and neutrophils are not present in the healthy heart but when there is tissue damage they can be found at those sites. Cardiac macrophages on the other hand reside in the interstitial spaces between the cardio myocytes and around endothelial cells. They are the major resident immune cell population in the healthy heart. They can be infected with HIV and have relatively long-life spans. They therefore may act as potential reservoirs. They are responsible for maintaining homeostasis, regulating electrical conduction, protection from infections and other tasks. One of their responses to infection or damage is the production of numerous inflammatory cytokines; TGF-B1, tumor necrosis factor-a are among those produced. These cytokines have been strongly associated with the production of fibrosis. In our model of chronic HIV disease, the HIV-1 Transgenic Rat, we have identified the toxic HIV protein GP-120 in the sera and in cells of stellate or elongated morphology in the heart. These cells have processes that interdigitate with the cardio myocytes. Immunocytochemistry demonstrated they are macrophage. We therefore hypotheses that the presence of GP-120 positive macrophages in the heart of this model may lead to myocyte death, fibrosis and loss of function. We examined the hearts of the HIV- 1 Transgenic Rat by histological examination with H&E, Trichrome and 1 mu thick resin sections. This approach allowed us to identify the different types of fibrosis. Three different types of cardiac fibrosis were identified: Interstitial, perivascular and replacement. This pathophysiological mechanism is a contributing factor in HIV related heart disease. In addition, areas of necrosis and inflammation were identified. Both T-cells and B-cells were identified by immunohistochemistry. This information reveals a possible pathway for the development of cardiac fibrosis which in time leads to heart failure. Identifying the potential mechanism(s) by which fibrosis occurs in an animal model, may allow for the development of cardiac protectors which together with antiviral therapy, may minimize this HIV noninfectious comorbidity. 2U54MDO13376-06A1, 5UL1GM118973, NIH/NINDS, 1 R29 NS31857-01A1 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.