Inhibition of NOX1 Mitigates Blood Pressure Increases in Elastin Insufficiency.

Published on Jan 1, 2021
· DOI :10.1093/FUNCTION/ZQAB015
Angela Troia3
Estimated H-index: 3
(NIH: National Institutes of Health),
Russell H Knutsen2
Estimated H-index: 2
(NIH: National Institutes of Health)
+ 8 AuthorsBeth A. Kozel22
Estimated H-index: 22
(NIH: National Institutes of Health)
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Abstract
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Elastin is a primary structural protein in the arterial wall that contributes to vascular mechanical properties and degrades with aging. Aging is associated with arterial stiffening and an increase...
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Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3–4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric ox...
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Abstract The small size and high heart rate of the neonatal mouse heart makes structural and functional characterisation particularly challenging. Here, we describe application of electrocardiogram-gated kilohertz visualisation (EKV) ultrasound imaging with high spatio-temporal resolution to non-invasively characterise the post-natal mouse heart during normal growth and regeneration after injury. The 2-D images of the left ventricle (LV) acquired across the cardiac cycle from post-natal day 1 (P...
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NEW FINDINGS: What is the central question of this study? Greater large artery stiffness is associated with dysfunctional resistance artery vasodilatory responses, impaired memory and greater risk of Alzheimer's disease. However, it is unknown whether stiffer large arteries affect cerebral and skeletal muscle feed artery responses to vasoconstrictors. What is the main finding and its importance? In a mouse model with greater large artery stiffness (Eln+/- ), we find an exacerbated vasoconstricto...
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Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. We summarize elastin protein biochemistry, self-association behavior, crosslinking process, and multi-step elastic fiber assembly that provide large arteries with their unique mechanical properties. We pres...
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Traumatic brain injury (TBI) is a prevalent disease with significant costs. Although progress has been made in understanding the complex pathobiology of focal lesions associated with TBI, questions remain regarding the diffuse responses to injury. Expression of the transient receptor potential melastatin 4 (Trpm4) channel, is linked to cytotoxic edema during hemorrhagic contusion expansion. However, little is known about Trpm4 following diffuse TBI. To explore Trpm4 expression in diffuse TBI, ra...
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Increased vascular stiffness correlates with higher risk of cardiovascular complications in aging adults. Elastin insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing. We used Eln+/- mice to test the hypothesis that pathologically increased vascular stiffness with concomitant arterial narrowing leads to decreased blood flow to end organs such as the brain. We also hyp...
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The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which...
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Nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase (NOX) is an enzyme complex with the sole function of producing superoxide anion and reactive oxygen species (ROS) at the expense of NADPH. Vital to the immune system as well as cellular signaling, NOX is also involved in the pathologies of a wide variety of disease states. Particularly, it an integral player in many neurological diseases, including stroke, TBI, and neurodegenerative diseases. Pathologically, NOX produces an excessive am...
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Original citation: J Clin Invest. 2016;126(1):50–67. doi:10.1172/JCI80761. Citation for this corrigendum: J Clin Invest. 2016;126(4):1607. doi:10.1172/JCI87425. During the assembly of Figure 10B, incorrect flow cytometry panels were inadvertently included for the Tgsm/p22phox + tempol sample. In addition, a different replicate is now provided for the Tgsm/p22phox sample in Figure 10A. The correct figure panels are below. The authors regret the errors.
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Reactive oxygen species (ROS), such as the superoxide anion or hydrogen peroxide, have been established over decades of research as, on the one hand, important and versatile molecules involved in a plethora of homeostatic processes and, on the other hand, as inducers of damage, pathologies and diseases. Which effects ROS induce, strongly depends on the cell type and the source, amount, duration and location of ROS production. Similar to cellular pH and calcium levels, which are both strictly reg...
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