TY - JOUR AU - Watanabe, Hirofumi AU - Martini, Alexandre G. AU - Brown, Robin Isadora AU - Liang, Xiuyin AU - Medrano, Silvia AU - Goto, Shin AU - Narita, Ichiei AU - Arend, Lois J. AU - Sequeira-Lopez, Maria Luisa S. AU - Gomez, R. Ariel T1 - Inhibition of the renin-angiotensin system causes concentric hypertrophy of renal arterioles in mice and humans PY - 2024/01/18/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.154337 VL - 6 IS - 24 UR - https://doi.org/10.1172/jci.insight.154337 PB - The American Society for Clinical Investigation ER -