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Inhibition of the renin-angiotensin system causes concentric hypertrophy of renal arterioles in mice and humans
- Source :
- JCI Insight
- Publication Year :
- 2021
-
Abstract
- Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease was caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surrounded the vessel walls and induced the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of β1 integrin prevented arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal vascular damage caused by the widespread use of inhibitors of the RAS.
- Subjects :
- medicine.medical_specialty
Concentric hypertrophy
Kidney
Muscle hypertrophy
Extracellular matrix
Renin-Angiotensin System
Mice
Fibrosis
Vascular Biology
Internal medicine
Chronic kidney disease
Renin–angiotensin system
Medicine
Endocrine system
Animals
Humans
Homeostasis
business.industry
Vascular disease
General Medicine
medicine.disease
Endocrinology
Nephrology
Hypertension
business
Research Article
Subjects
Details
- ISSN :
- 23793708
- Volume :
- 6
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- JCI insight
- Accession number :
- edsair.doi.dedup.....4ef92b8dfee2d65b07e05b68ea47a6e9