DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells
Authors' conclusion
The prostaglandin D2/DP1 axis suppresses age-related Th1 activation and subsequent hypertensive response in male mice through increase of NEDD4L-mediated T-bet degradation by ubiquitination.
Study context
- Population
- Young and older male participants (peripheral blood CD4+ T cells); aged male mice
Methodological detailsMouse BP measured by invasive telemetric monitor
- Mouse BP measured by invasive telemetric monitor
Main finding
As reported in the abstract
- Prostaglandin D2/DP1 axis downregulated in CD4+ T cells from older humans and aged mice
- DP1 deletion in CD4+ T cells augmented age-related hypertension in aged male mice (more T helper (Th1) cytokine secretion, vascular remodeling, CD4+ T-cell infiltration, vascular/renal superoxide)
- Forced exogenous DP1 expression in T cells retarded age-associated hypertension in mice by reducing Th1 cytokine secretion
- TNF-α neutralization or interferon γ deletion ameliorated age-related hypertension in CD4+ T-cell DP1-deletion mice
- DP1 inhibited Th1 activity via PKA/p-Sp1/NEDD4L pathway-mediated T-bet ubiquitination
- T-bet deletion or forced NEDD4L expression in CD4+ T cells attenuated age-related hypertension in CD4+ T cell-specific DP1-deficient mice
- DP1 activation by BW245C prevented age-associated BP elevation and reduced vascular/renal superoxide in male mice
Original publication
DP1 Activation Reverses Age-Related Hypertension Via NEDD4L-Mediated T-Bet Degradation in T Cells. Circulation. Published 2 January 2020. doi:10.
Summarised from the published abstract; every number is checked against it