CD4 + T Cells Expressing Viral Proteins Induce HIV-Associated Endothelial Dysfunction and Hypertension Through Interleukin 1α–Mediated Increases in Endothelial NADPH Oxidase 1
Authors' conclusion
We provide the first evidence that CD4+ T cells expressing HIV viral proteins induced hypertension through IL-1α-mediated increases in vascular NOX1, which impairs endothelial function in males and females.
Study context
- Population
- Tg26 mice and WT mice; aorta specimens discarded from people living with HIVmale and female mice
- Comparison
- Tg26 vs WT
- Outcome
- Endothelium-dependent relaxation and BP
Methodological detailsTg26 mouse model of HIV, bone marrow transplantation, adoptive transfer of CD4+ T cells, human aorta specimens, male and female mice
- Tg26 mouse model of HIV
- Bone marrow transplantation
- Adoptive transfer of CD4+ T cells
- Human aorta specimens
- Male and female mice
Main finding
As reported in the abstract
Endothelium-dependent relaxation and BP with CD4+ T cells expressing viral proteins
- Intact Tg26 mice and mice receiving bone marrow transplantation (BMT) (Tg26→WT) or CD4+ T cells from Tg26 mice display impaired endothelium-dependent relaxation and hypertension
- BMT from WT mice into Tg26 mice, inhibition of T cell activation, and CD4+ T cell depletion restored endothelial function and BP in Tg26 mice
- Exposure of WT aortas to Tg26 CD4+ T cells impaired endothelium-dependent relaxation, blocked by IL-1α-neutralizing antibody
Further findings
Cytokine profiling
- Tg26 mice, Tg26→WT and Tg26 CD4+ T cells consistently exhibit high IL-1α levels with no significant increase in other cytokines
- BMT from WT mice into Tg26 mice reduced IL-1α levels
IL-1α neutralisation
- Reduced BP and restored endothelial function in Tg26 mice
Vascular NOX1
- Tg26 and Tg26→WT aorta exhibit high NOX1 expression
- IL-1α exposure increased NOX1 in human microvascular endothelial cells
- NOX1 blockade restored endothelial function in Tg26 and Tg26→WT arteries
- NOX1 deficiency protected against Tg26 BMT-induced impaired endothelium-dependent relaxation and hypertension
NOX1 in human aorta
- Aortas from people living with HIV exhibit high NOX1 levels
- Exposure of human aorta to Tg26 T cells increased NOX1 expression
Original publication
CD4 + T Cells Expressing Viral Proteins Induce HIV-Associated Endothelial Dysfunction and Hypertension Through Interleukin 1α–Mediated Increases in Endothelial NADPH Oxidase 1. Circulation. Published 5 February 2025. doi:10.
Summarised from the published abstract; every number is checked against it