肾素-血管紧张素系统
细胞外基质
纤维化
肌肉肥大
内科学
内分泌学
肾
血管紧张素II
血管平滑肌
生物
医学
细胞生物学
血压
平滑肌
作者
Hirofumi Watanabe,Alexandre G Martini,Evan Brown,Xiuyin Liang,Silvia Medrano,Shin Goto,Ichiei Narita,Lois J. Arend,Maria Luisa S. Sequeira‐Lopez,R. Ariel Gómez
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2021-12-22
卷期号:6 (24)
被引量:17
标识
DOI:10.1172/jci.insight.154337
摘要
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.
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