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Sympathoexcitation ...
Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus
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Wang, Renjun (author)
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Huang, Qian (author)
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Zhou, Rui (author)
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Dong, Zengxiang (author)
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Qi, Yunfeng (author)
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Li, Hua (author)
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Wei, Xiaowei (author)
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Wu, Hui (author)
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Wang, Huiping (author)
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Wilcox, Christopher S (author)
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- Hultström, Michael, 1978- (author)
- Uppsala universitet,Integrativ Fysiologi,Anestesiologi och intensivvård
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Zhou, Xiaofu (author)
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Lai, En Yin (author)
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(creator_code:org_t)
- 2016
- 2016
- English.
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In: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 9:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND: Chronic heart failure (CHF) increases sympathoexcitation through angiotensin II (ANG II) receptors (AT1R) in the paraventricular nucleus (PVN). Recent publications indicate both γ-aminobutyric acid B-type receptor 1 (GABBR1) and microRNA-7b (miR-7b) are expressed in the PVN. We hypothesized that ANG II regulates sympathoexcitation through homeobox D10 (HoxD10), which regulates miR-7b in other tissues.METHODS AND RESULTS: Ligation of the left anterior descendent coronary artery in rats caused CHF and sympathoexcitation. PVN expression of AT1R, HoxD10, and miR-7b was increased, whereas GABBR1 was lower in CHF. Infusion of miR-7b in the PVN caused sympathoexcitation in control animals and enhanced the changes in CHF. Antisense miR-7b infused in PVN normalized GABBR1 expression while attenuating CHF symptoms, including sympathoexcitation. A luciferase reporter assay detected miR-7b binding to the 3' untranslated region of GABBR1 that was absent after targeted mutagenesis. ANG II induced HoxD10 and miR-7b in NG108 cells, effects blocked by AT1R blocker losartan and by HoxD10 silencing. miR-7b transfection into NG108 cells decreased GABBR1 expression, which was inhibited by miR-7b antisense. In vivo PVN knockdown of AT1R attenuated the symptoms of CHF, whereas HoxD10 overexpression exaggerated them. Finally, in vivo PVN ANG II infusion caused dose-dependent sympathoexcitation that was abrogated by miR-7b antisense and exaggerated by GABBR1 silencing.CONCLUSIONS: There is an ANG II/AT1R/HoxD10/miR-7b/GABBR1 pathway in the PVN that contributes to sympathoexcitation and deterioration of cardiac function in CHF.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- gamma-aminobutyric acid; homeobox D10; microRNA-7b; paraventricular nucleus
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Wang, Renjun
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Huang, Qian
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Zhou, Rui
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Dong, Zengxiang
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Qi, Yunfeng
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Li, Hua
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show more...
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Wei, Xiaowei
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Wu, Hui
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Wang, Huiping
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Wilcox, Christop ...
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Hultström, Micha ...
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Zhou, Xiaofu
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Lai, En Yin
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
- Articles in the publication
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Circulation Hear ...
- By the university
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Uppsala University