Cell-Specific Inducible Human Apolipoprotein L1 (APOL1) Risk Variant Expression in Mice Causes Hypertension and Renal Damage
Authors' conclusion
These findings indicate a role of G2APOL1 in hypertension development through STING and endothelin 1 activation, offering new precision therapeutics for addressing hypertension in Black people carrying APOL1 RVs.
Study context
- Population
- Patient kidney samples and transgenic mice with podocyte- or endothelium-specific APOL1 expression
- Comparison
- G2APOL1 risk variant vs G0 reference allele
- Outcome
- Causal role of APOL1 RVs in hypertension and renal damage
Methodological detailshuman kidney samples, transgenic mouse models, in vitro primary cell experiments
- Human kidney samples
- Transgenic mouse models
- In vitro primary cell experiments
Main finding
As reported in the abstract
APOL1 expression and RV-mediated hypertension and kidney damage
- In the human kidney, APOL1 highly expressed by glomerular podocytes and endothelial cells
- Podocyte-specific G2APOL1 mice developed severe secondary hypertension after albuminuria and kidney disease; G0 mice did not
- Endothelium-specific G2APOL1 mice developed mild hypertension with aging, exacerbated after unilateral nephrectomy and subsequent high-salt diet, with slight alteration in kidney function
- APOL1 RV activates cytosolic nucleotide sensor STING, leading to increased production of endothelin 1 (in vitro and in vivo)
- Endothelium-specific STING knockout or endothelin inhibitor treatment protected from G2APOL1 RV-mediated hypertension
Original publication
Cell-Specific Inducible Human APOL1 Risk Variant Expression in Mice Causes Hypertension and Renal Damage. Circulation. Published 11 December 2025. doi:10.
Summarised from the published abstract; every number is checked against it