Due to advances in antiretroviral therapy (ART), more than 50% of patients with HIV are currently older than 50 years old, and aging appears accelerated in persons living with HIV (PLWH), resulting in higher incidence of chronic health conditions in these patients. Many more patients with HIV now die from other comorbid conditions than the immunodeficiency caused by the infection itself. Among these comorbid conditions, cardiovascular (CV) disease (CVD) has become increasingly common, even when HIV replication is fully suppressed by ART. One of the CV abnormalities more commonly found in PLWH than uninfected persons is heart failure (HF) with preserved ejection fraction (HFpEF), defined as HF with left ventricular ejection fraction of 50% or more. The development of HFpEF in the general population is associated with an increase in all-cause mortality, highlighting the clinical significance of this disorder. The mechanism for the development of HFpEF in PLWH is not totally understood, but direct effects of HIV, chronic inflammation, genetic predisposition, and side effects of ART have been proposed as possible mechanisms. A recent report provided a state-of-the-art system to study HFpEF in SIV-infected rhesus macaques and cardiomyocytes form these animals. However, there are no in vitro or in vivo models to study HIV-mediated HFpEF, or to assess the effectiveness of CV drugs using a less costly system than clinical trials. We are addressing this fundamental gap in knowledge by developing a more feasible human in vitro model that could be applicable for HFpEF in uninfected as well as PLWH, and will use novel approaches using human induced pluripotent stem cells (hiPSC)-derived cardiomyocytes (hiPSC-CM) to study the pathogenesis of HFpEF in HIV-infected individuals.
|Effective start/end date||1/1/18 → 12/31/21|
- National Heart, Lung, and Blood Institute (5R01HL140973-04)