With prompt diagnosis and the right treatment, people living with HIV can live long, healthy lives. In recent years, however, survival gains among people living with HIV have revealed a new concern – an increased incidence of early cardiovascular disease associated with long-term HIV.
Why cardiovascular disease is likely to develop a decade earlier in HIV-positive people than in non-HIV-positive people is unclear. But now, with the support of a National Institute on Drug Abuse Avenir Award, part of the National Institutes of Health (NIH) Director’s New Innovator Award (DP2) program, researchers at the Lewis Katz School of Medicine in Temple University hope to gain new insight into the relationship between HIV and heart disease, as well as the effect of substance use on this relationship.
The DP2 award—a first for Temple—is highly competitive, supporting transformative research in NIH-designated high priority areas. The funding, $2,377,500 over four years, will support studies led by Allison M. Andrews, PhD, assistant professor in the Department of Pathology and Laboratory Medicine at Temple University’s Lewis Katz School of Medicine. The research will specifically focus on elucidating the effects of HIV and cocaine use on the bone marrow blood barrier, a physiological boundary that prevents immature blood cells from escaping from the bone marrow.
We are particularly interested in studying changes in the bone marrow vasculature, microenvironment, and stem cell niche that result from HIV and drugs, such as cocaine.”
Dr. Allison M. Andrews, PhD, Assistant Professor, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University
Early-onset cardiovascular disease in people living with HIV is associated with increased infiltration of immune cells into the wall of blood vessels to form unstable plaques. These immune cells mature from hematopoietic stem cells (HSCs) in the bone marrow niche. It is perhaps no coincidence that the bone marrow is also a reservoir for HIV.
Dr. Andrews and others suspect that HIV somehow alters the local marrow microenvironment and HSC development to ultimately facilitate HSC differentiation into activated immune cells. They hypothesize that cocaine, which exacerbates HIV pathology, may amplify the effects of HIV on the bone marrow or enable HSC differentiation via an entirely different mechanism.
Dr. Andrews plans to investigate these ideas through the proposed development of a human bone marrow chip, in which human bone marrow stem cells are embedded in a gel matrix that essentially mimics the 3D nature of bone marrow tissue. . Each chip is about the size of a thumb drive. Using microCT and other advanced imaging techniques, Dr. Andrews and his colleagues also plan to map the 3D architecture of the bone marrow vasculature of HIV-infected mice.
“Through these studies, we aim to create a novel human 3D tissue model of bone marrow vasculature for the study of HIV pathogenesis,” Dr. Andrews added. “The technology is also a promising tool for predictive modeling that could translate clinically into the development of new strategies for the care of people living with HIV who face cardiovascular disease.”
Temple University Health System