1. Mineralocorticoid receptor: A hidden culprit for hemodialysis vascular access dysfunction
- Author
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Bohan Chen, Zhangsuo Liu, Pei Wang, Andrew S. Brem, Lance D. Dworkin, and Rujun Gong
- Subjects
0301 basic medicine ,Vascular smooth muscle ,Intimal hyperplasia ,Mineralocorticoid receptor ,lcsh:Medicine ,Review ,VCAM-1, vascular cell adhesion molecule-1 ,Muscle, Smooth, Vascular ,chemistry.chemical_compound ,0302 clinical medicine ,ESRD, end-stage renal disease ,Cell Movement ,Medicine ,Arteriovenous fistula failure ,Aldosterone ,lcsh:R5-920 ,EPCs, endothelial progenitor cells ,eNOS, endothelial nitric oxide synthase ,General Medicine ,MCP-1, monocyte chemotactic protein-1 ,ECM, extracellular matrix ,3. Good health ,VSMC, vascular smooth muscle cells ,030220 oncology & carcinogenesis ,WSS, wall shear stress ,Cell activation ,lcsh:Medicine (General) ,Signal Transduction ,Myocytes, Smooth Muscle ,Macrophage polarization ,Nitric Oxide ,Hemodialysis vascular access dysfunction ,General Biochemistry, Genetics and Molecular Biology ,α-SMA, α-smooth muscle actin ,End stage renal disease ,IH, intimal hyperplasia ,03 medical and health sciences ,Renal Dialysis ,AT1R, Angiotensin II type 1 receptor ,Ang II, Angiotensin II ,Humans ,VCAM-1 ,Cell Proliferation ,NO, nitric oxide ,Hyperplasia ,AVF, arteriovenous fistula ,business.industry ,CKD, chronic kidney disease ,lcsh:R ,MR, mineralocorticoid receptor ,medicine.disease ,Fibrosis ,Angiotensin II ,IL, interleukin ,Receptors, Mineralocorticoid ,030104 developmental biology ,AVG, arteriovenous grafts ,chemistry ,Cancer research ,MMPs, matrix metalloproteinases ,Reactive Oxygen Species ,Tunica Intima ,business ,SGK1, serum-and-glucocorticoid regulated kinase1 - Abstract
Hemodialysis vascular access dysfunction is a common and intractable problem in clinical practice with no definitive therapy yet available. As a key mediator of vascular and cardiac maladaptive remodeling, mineralocorticoid receptor (MR) plays a pivotal role in vascular fibrosis and intimal hyperplasia (IH) and is potentiated locally in hemodialysis vascular access following diverse injuries, like barotrauma, cannulation and shear stress. MR-related genomic and non-genomic pathways are responsible for triggering vascular smooth muscle cell activation, proliferation, migration and extracellular matrix overproduction. In endothelial cells, MR signaling diminishes nitric oxide production and its bioavailability, but amplifies reactive oxygen species, leading to an inflammatory state. Moreover, MR favors macrophage polarization towards a pro-inflammatory phenotype. In clinical settings like post-angioplasty or stenting restenosis, the beneficial effect of MR antagonists on vascular fibrosis and IH has been validated. In aggregate, therapeutic targeting of MR may provide a new avenue to prevent hemodialysis vascular access dysfunction., Highlights • MR signaling is instrumental in both insufficient outward remodeling and exuberant inward remodeling of AVF. • The effects of MR in VSMC, endothelial cell, and macrophage act synergistically to promote IH and vascular fibrosis in AVF. • Pharmacological targeting of MR represents a novel therapeutic strategy to prevent hemodialysis vascular access dysfunction.
- Published
- 2019