Inhibition of the renin-angiotensin system causes concentric hypertrophy of renal arterioles in mice and humans

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 beta(1) 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.

Automated summary

By studying mice and human subjects, it was found that deletion of renin or inhibition of the RAS may lead to concentric thickening of intrarenal arteries and arterioles, causing severe diseases such as blood flow obstruction, focal ischemia, and fibrosis. This is due to the expansion and transformation of renin cells, highlighting the importance of further morphological studies in humans to understand the extent of renal vascular damage from the use of RAS inhibitors.