Am J Physiol Heart Circ Physiol
Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland.
Published: November 2019
Vascular stiffness plays a key role in the pathogenesis of hypertension. Recent studies indicate that the age-associated reduction in miR-181b levels in vascular smooth muscle cells (VSMCs) contributes to increased vascular stiffness. As these findings suggest that inhibiting degradation of miR-181b might prevent vascular stiffening, we have assessed whether the microRNA-degrading translin/trax (TN/TX) complex mediates degradation of miR-181b in the aorta.We found that TN mice display elevated levels of miR-181b expression in the aorta. Therefore, we tested whether TN deletion prevents vascular stiffening in a mouse model of hypertension, induced by chronic high-salt intake (4%NaCl in drinking water for 3 wk; HSW). TN mice subjected to HSW stress do not show increased vascular stiffness, as monitored by pulse wave velocity and tensile testing. The protective effect of TN deletion in the HSW paradigm appears to be mediated by its ability to increase miR-181b in the aorta since HSW decreases levels of miR-181b in WT mice, but not in TN KO mice. We demonstrate for the first time that interfering with microRNA degradation can have a beneficial impact on the vascular system and identify the microRNA-degrading TN/TX RNase complex as a potential therapeutic target in combatting vascular stiffness. While the biogenesis and mechanism of action of mature microRNA are well understood, much less is known about the regulation of microRNA via degradation. Recent studies have identified the protein complex, translin(TN)/trax(TX), as a microRNA-degrading enzyme. Here, we demonstrate that TN/TX is expressed in vascular smooth muscle cells. Additionally, deletion of the TN/TX complex selectively increases aortic miR-181b and prevents increased vascular stiffness caused by ingestion of high-salt water. To our knowledge, this is first report describing the role of a microRNA RNAse in cardiovascular biology or pathobiology.
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http://dx.doi.org/10.1152/ajpheart.00153.2019 | DOI Listing |
JACC Asia
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Department of Regenerative Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Vascular function is impaired by conditions such as hypertension, dyslipidemia, and diabetes as well as coronary risk factors including age, smoking, obesity, menopause and physical inactivity. Measurement of vascular function is useful not only for assessment of atherosclerosis itself but also in many other aspects such as understanding the pathophysiology, assessing treatment efficacy, and predicting prognosis of cardiovascular events. It is therefore important to accurately assess the extent of vascular function.
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Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing, 400044, P. R. China.
Decellularized artificial blood vessels prepared using physical and chemical methods often exhibit limitations, including poor mechanical performance, susceptibility to inflammation and calcification, and reduced patency. Cross-linking techniques can enhance the stiffness, as well as anti-inflammatory and anti-calcification properties of decellularized vessels. However, conventional cross-linking methods fail to effectively alleviate residual stress post-decellularization, which significantly impacts the patency and vascular remodeling following the implantation of artificial vessels.
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Unidad de Investigación en Atención Primaria de Salamanca (APISAL), Gerencia de Atención Primaria de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, España; Red de Investigación en Cronicidad, Atención Primaria y Promoción de la Salud (RICAPPS) Salamanca, España; Departamento de Medicina, Universidad de Salamanca, Salamanca, España.
Introduction And Objectives: To analyse the increase of arterial stiffness over a five-year period and its relationship with cardiovascular risk factors and sex-based differences in a Spanish population without cardiovascular disease.
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Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
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