Overexpression of GRK2 in vascular smooth muscle leads to inappropriate hypertension and acute heart failure as in clinical scenario 1

• Material Type: 博士論文
• Title: Overexpression of GRK2 in vascular smooth muscle leads to inappropriate hypertension and acute heart failure as in clinical scenario 1
• Author/Editor: Yano, Hiroki; Onoue, Kenji; Tokinaga, Shiho; Ioka, Tomoko; Ishihara, Satomi; Hashimoto, Yukihiro; Nakada, Yasuki; Nakagawa, Hitoshi; Ueda, Tomoya; Seno, Ayako; Nishida, Taku; Watanabe, Makoto; Saito, Yoshihiko
• Author Heading: Yano, Hiroki; Onoue, Kenji; Tokinaga, Shiho; Ioka, Tomoko; Ishihara, Satomi; Hashimoto, Yukihiro; Nakada, Yasuki; Nakagawa, Hitoshi; Ueda, Tomoya; Seno, Ayako; Nishida, Taku; Watanabe, Makoto; Saito, Yoshihiko
• Publication, Distribution, etc.: Springer Nature（Nature Portfolio）
• Publication Date: 2023
• Publication Date (W3CDTF): 2023
• Alternative Title: GRK2を血管平滑筋で過剰発現させることで過度な血圧上昇ひいてはCS1急性心不全様の病態を呈した
• Periodical title: Scientific Reports
• No. or year of volume/issue: 13
• Volume: 13
• Pages: Article number:7707-
• ISSN (Periodical Title): ISSN : 2045-2322
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2023-09-29
• Dissertation Number: 甲第889号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Cardiology; Pathogenesis
• Target Audience: 一般
• Note (General): type:Thesis; Clinical scenario 1 (CS1) is acute heart failure (HF) characterized by transient systolic blood pressure (SBP) elevation and pulmonary congestion. Although it is managed by vasodilators, the molecular mechanism remains unclear. The sympathetic nervous system plays a key role in HF, and desensitization of cardiac β-adrenergic receptor (AR) signaling due to G protein-coupled receptor kinase 2 (GRK2) upregulation is known. However, vascular β-AR signaling that regulates cardiac afterload remains unelucidated in HF. We hypothesized that upregulation of vascular GRK2 leads to pathological conditions similar to CS1. GRK2 was overexpressed in vascular smooth muscle (VSM) of normal adult male mice by peritoneally injected adeno-associated viral vectors driven by the myosin heavy chain 11 promoter. Upregulation of GRK2 in VSM of GRK2 overexpressing mice augmented the absolute increase in SBP (+ 22.5 ± 4.3 mmHg vs. + 36.0 ± 4.0 mmHg, P < 0.01) and lung wet weight (4.28 ± 0.05 mg/g vs. 4.76 ± 0.15 mg/g, P < 0.01) by epinephrine as compared to those in control mice. Additionally, the expression of brain natriuretic peptide mRNA was doubled in GRK2 overexpressing mice as compared to that in control mice (P < 0.05). These findings were similar to CS1. GRK2 overexpression in VSM may cause inappropriate hypertension and HF, as in CS1.; 権利情報：© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The version of record of this article, first published in Scientific Reports, is available online at Publisher’s website: https://doi.org/10.1038/s41598-023-34209-5; identifier:Scientific Reports. 2023 May, vol.13, article number:7707; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4219; identifier:Scientific Reports, 13: Article number:7707
• Source: fulltext; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4219/1/K889%20full.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4219/2/K889_abstract.pdf; http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/4219/3/K889_review.pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1038/s41598-023-34209-5
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU