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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
- Article/chapterEnglish2016
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LIBRIS-ID:oai:DiVA.org:uu-272536
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-272536URI
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https://doi.org/10.1161/CIRCHEARTFAILURE.115.002261DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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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-Uppsala universitet,Integrativ Fysiologi,Anestesiologi och intensivvård(Swepub:uu)mihul498
(author)
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Zhou, Xiaofu
(author)
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Lai, En Yin
(author)
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Uppsala universitetIntegrativ Fysiologi
(creator_code:org_t)
Related titles
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In:Circulation Heart Failure9:11941-32891941-3297
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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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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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- 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
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Circulation Hear ...
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Uppsala University