What You Should Know:
– Two new National Institutes of Health grants, totaling $5.7 million, are aimed at helping scientists at the Medical College of Georgia at Augusta University better understand the mechanisms of two cardiovascular complications associated with HIV.
– Thanks to the advent of combination antiretroviral therapy (cART), which uses a combination of three or more drugs to stop the virus from replicating in the body, life expectancy of people living with HIV has dramatically increased. In fact, most people living with HIV no longer die from the opportunistic disease but instead from cardiovascular disease.
NIH Grants Advance Understanding of HIV-Associated Cardiovascular and Pulmonary Complications
Researchers at the Medical College of Georgia (MCG) are making significant strides in understanding the mechanisms underlying cardiovascular and pulmonary complications in people living with HIV. Two newly awarded grants from the National Institutes of Health (NIH), totaling $5.7 million, support their groundbreaking work.
Hypertension in HIV: Investigating the Role of HIV-Derived Proteins
Eric Belin de Chantemèle, PhD, from the MCG Vascular Biology Center, leads a $2.7 million NIH-funded study focusing on the early onset and high prevalence of hypertension in people with HIV. Key findings from his work include:
- Persistent HIV Proteins: Despite combination antiretroviral therapy (cART) and controlled viral loads, circulating HIV-derived proteins contribute to hypertension.
- Mechanisms of Vascular Dysfunction: These proteins increase Interleukin-1 alpha (IL-1 alpha), a pro-inflammatory cytokine, impairing endothelium-dependent vascular relaxation and leading to elevated blood pressure.
- Therapeutic Insights: Inhibiting T cell activation in a transgenic mouse model of HIV restored normal blood pressure and improved endothelial cell function.
Future research will explore IL-1 alpha’s role in vascular aging and its promotion of hypertension through excessive reactive oxygen species, which damage endothelial cells.
Pulmonary Vascular Disease: Structural Changes in Pulmonary Arteries
Belin de Chantemèle and Laszlo Kovacs, PhD, of MCG’s Department of Pharmacology and Toxicology, are co-principal investigators on a $3 million grant examining pulmonary vascular disease (PVD), a severe cardiovascular complication of HIV. Their research focuses on:
- Vascular Remodeling: HIV-derived proteins are hypothesized to drive structural changes in pulmonary arteries, a hallmark of PVD.
- Biomarker Identification: RNA sequencing identified Podnl1 as a novel biomarker for PVD, with elevated levels observed in HIV-infected transgenic and wild-type mice and in human lung tissue from cART-treated individuals with HIV.
- Experimental Validation: Bone marrow transplants from HIV-transgenic mice to wild-type mice induced similar cardiopulmonary complications, supporting the role of viral proteins in disease progression.
Impact and Future Directions
These studies aim to elucidate the molecular mechanisms linking HIV to cardiovascular and pulmonary complications. The findings could lead to new diagnostic tools, biomarkers, and therapeutic targets, ultimately improving the care and outcomes for people living with HIV