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01-10-2020 | Stroke | Original Article

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis

Authors: Ning Xiao, Tian-long Liu, Hao Li, Hao-chen Xu, Jing Ge, Hong-yan Wen, Cong-xia Bai, Li Song, Ying-ying Sun, Yin-hui Zhang, Ru-tai Hui, Wei-hua Song, Jing-zhou Chen

Published in: Translational Stroke Research | Issue 5/2020

Abstract

Intracerebral hemorrhage (ICH) is a catastrophic stroke with high mortality, and the mechanism underlying ICH is largely unknown. Previous studies have shown that high serum uric acid (SUA) levels are an independent risk factor for hypertension, cardiovascular disease (CVD), and ischemic stroke. However, our metabolomics data showed that SUA levels were lower in recurrent intracerebral hemorrhage (R-ICH) patients than in ICH patients, indicating that lower SUA might contribute to ICH. In this study, we confirmed the association between low SUA levels and the risk for recurrence of ICH and for cardiac-cerebral vascular mortality in hypertensive patients. To determine the mechanism by which low SUA effects ICH pathogenesis, we developed the first low SUA mouse model and conducted transcriptome profiling of the cerebrovasculature of ICH mice. When combining these assessments with pathological morphology, we found that low SUA levels led to ICH in mice with angiotensin II (Ang II)–induced hypertension and aggravated the pathological progression of ICH. In vitro, our results showed that p-Erk1/2-MMP axis were involved in the low UA-induce degradation of elastin, and that physiological concentrations of UA and p-Erk1/2-specific inhibitor exerted a protective role. This is the first report describing to the disruption of the smooth muscle cell (SMC)-elastin contractile units in ICH. Most importantly, we revealed that the upregulation of the p-Erk1/2-MMP axis, which promotes the degradation of elastin, plays a vital role in mediating low SUA levels to exacerbate cerebrovascular rupture during the ICH process.

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Title: Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis
Authors: Ning Xiao
Tian-long Liu
Hao Li
Hao-chen Xu
Jing Ge
Hong-yan Wen
Cong-xia Bai
Li Song
Ying-ying Sun
Yin-hui Zhang
Ru-tai Hui
Wei-hua Song
Jing-zhou Chen
Publication date: 01-10-2020
Publisher: Springer US
Keyword: Stroke
Published in: Translational Stroke Research / Issue 5/2020
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-020-00791-3

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Low Serum Uric Acid Levels Promote Hypertensive Intracerebral Hemorrhage by Disrupting the Smooth Muscle Cell-Elastin Contractile Unit and Upregulating the Erk1/2-MMP Axis

Abstract

At a glance: The ONWARDS insulin icodec trials

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Abstract

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