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High intraluminal pressure promotes vascular inflammation via caveolin-1

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journal contribution
posted on 2021-05-12, 00:23 authored by DL Michell, WA Shihata, KL Andrews, NAZ Abidin, AM Jefferis, AK Sampson, NG Lumsden, O Huet, MO Parat, GL Jennings, RG Parton, KJ Woollard, DM Kaye, JPF Chin-Dusting, Andrew MurphyAndrew Murphy
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.


This study was supported by a National Health and Medical Research Council of Australia program grant NHMRC#1036352 (JCD) and postgraduate scholarship NHMRC#1017847 (DLM) and supported in part by the Victorian Government's Operational Infrastructure Support Program. RGP is supported by grants and a fellowship from the National Health and Medical Research Council of Australia (grants APP1140064 and APP1150083 and fellowship APP1156489). AJM is supported by a CSL Centenary Award.


Publication Date



Scientific Reports





Article Number

ARTN 5894







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