High intraluminal pressure promotes vascular inflammation via caveolin-1.

Autor:	Michell DL; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Department of Medicine, Monash University, Clayton, VIC, Australia., Shihata WA; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. waled.shihata@baker.edu.au.; Department of Medicine, Monash University, Clayton, VIC, Australia. waled.shihata@baker.edu.au.; Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia. waled.shihata@baker.edu.au., Andrews KL; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.; Department of Pharmacology, Monash University, Clayton, VIC, Australia., Abidin NAZ; Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.; Department of Pharmacology, Monash University, Clayton, VIC, Australia., Jefferis AM; Department of Pharmacology, Monash University, Clayton, VIC, Australia., Sampson AK; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Lumsden NG; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Huet O; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Parat MO; School of Pharmacy, University of Queensland, St Lucia, QLD, Australia., Jennings GL; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Parton RG; Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, University of Queensland, St Lucia, QLD, Australia., Woollard KJ; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, London, UK., Kaye DM; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia., Chin-Dusting JPF; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.; Department of Medicine, Monash University, Clayton, VIC, Australia.; Cardiovascular Disease Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.; Department of Pharmacology, Monash University, Clayton, VIC, Australia., Murphy AJ; Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2021 Mar 15; Vol. 11 (1), pp. 5894. Date of Electronic Publication: 2021 Mar 15.
DOI:	10.1038/s41598-021-85476-z
Abstrakt:	The aetiology and progression of hypertension involves various endogenous systems, such as the renin angiotensin system, the sympathetic nervous system, and endothelial dysfunction. Recent data suggest that vascular inflammation may also play a key role in the pathogenesis of hypertension. This study sought to determine whether high intraluminal pressure results in vascular inflammation. Leukocyte adhesion was assessed in rat carotid arteries exposed to 1 h of high intraluminal pressure. The effect of intraluminal pressure on signaling mechanisms including reactive oxygen species production (ROS), arginase expression, and NFĸB translocation was monitored. 1 h exposure to high intraluminal pressure (120 mmHg) resulted in increased leukocyte adhesion and inflammatory gene expression in rat carotid arteries. High intraluminal pressure also resulted in a downstream signaling cascade of ROS production, arginase expression, and NFĸB translocation. This process was found to be angiotensin II-independent and mediated by the mechanosensor caveolae, as caveolin-1 (Cav1)-deficient endothelial cells and mice were protected from pressure-induced vascular inflammatory signaling and leukocyte adhesion. Cav1 deficiency also resulted in a reduction in pressure-induced glomerular macrophage infiltration in vivo. These findings demonstrate Cav1 is an important mechanosensor in pressure-induced vascular and renal inflammation.
Databáze:	MEDLINE
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