(Philadelphia, Pennsylvania) – 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, in the amount of $2,377,500 over four years, will support studies conducted by Allison M. Andrews, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at the Lewis Katz School of Medicine at Temple University. 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 the changes in the bone marrow vasculature, microenvironment and stem cell niche that result from HIV and drugs, such as cocaine,” Dr Andrews said.
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 3D human 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.
The research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number DP2DA056172. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About the Lewis Katz School of Medicine
Founded in 1901, the Lewis Katz School of Medicine at Temple University attracts students and faculty committed to advancing the health of individuals and populations through patient care, research, education, and culturally competent services. The school confers the medical degree; Master’s and doctoral degrees in biomedical sciences; the master’s degree in urban bioethics; the Masters in Physician Assistant Studies; a certificate in narrative medicine; a non-degree post-baccalaureate program; several dual degree programs with other Temple University schools; continuing medical education programs; and in partnership with Temple University Hospital, 40 residency and fellowship programs for physicians. The School also manages a strong portfolio of publicly and privately funded transdisciplinary studies aimed at advancing the prevention, diagnosis and treatment of disease – with specialized research centers focusing on heart disease, cancer, substance use disorders, metabolic diseases and other regional diseases and national health priorities. To learn more about the Lewis Katz School of Medicine, please visit: medicine.temple.edu.
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