20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells
Abstract In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II...
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2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85992-2 |
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| author | Jingyi Han Jiaojiao Li Lianlian Liu Kaiyuan Li Chun Zhang Yong Han |
| author_facet | Jingyi Han Jiaojiao Li Lianlian Liu Kaiyuan Li Chun Zhang Yong Han |
| author_sort | Jingyi Han |
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| description | Abstract In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II on CYP4A expression and 20-HETE production in H9c2 cells using RT-qPCR, Western blot, and ELISA. The role of 20-HETE in Ang II-induced cardiac hypertrophy was examined using DHE, MitoSOX, and JC-1 staining to evaluate reactive oxygen species (ROS) generation and mitochondrial membrane potential changes. The ERK/Akt and CaN/NFAT3 signaling pathways were analyzed through Western blot. Ang II was found to promote CYP4A expression and 20-HETE production in H9c2 cells via an AT1 receptor-dependent mechanism. Additionally, the upregulation of AT1 receptor expression by 20-HETE further confirms its facilitatory effect on the Ang II signaling pathway. Inhibition of 20-HETE synthesis or blockade of its receptor, G-protein-coupled receptor 75 (GPR75), significantly reversed Ang II-induced cardiac hypertrophy. This reversal was closely associated with 20-HETE-induced ROS production, oxidative stress, and activation of the Ca2+/CaN/NFAT3 signaling pathway. This study demonstrated that 20-HETE mediated Ang II-induced cardiac hypertrophy and, for the first time, highlighted the significant role of the GPR75 receptor in this process. These findings suggested that targeting 20-HETE reduction or blocking its receptor action could offer a novel therapeutic approach for cardiovascular diseases associated with Ang II. |
| format | Article |
| id | doaj-art-2ba5ad9085524b82adc23ba7c42205d1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-2ba5ad9085524b82adc23ba7c42205d12025-01-19T12:19:47ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-85992-220-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cellsJingyi Han0Jiaojiao Li1Lianlian Liu2Kaiyuan Li3Chun Zhang4Yong Han5Department of Physiology, Zunyi Medical UniversityDepartment of Physiology, Zunyi Medical UniversityDepartment of Physiology, Zunyi Medical UniversityDepartment of Physiology, Zunyi Medical UniversityDepartment of Physiology, Zunyi Medical UniversityDepartment of Physiology, Zunyi Medical UniversityAbstract In the vascular system, angiotensin II (Ang II) mediated vasoconstriction by inducing the production of 20-hydroxyeicosatetraenoic acid (20-HETE). However, the role of 20-HETE in Ang II-induced cardiac dysfunction had yet to be fully elucidated. This study investigated the effects of Ang II on CYP4A expression and 20-HETE production in H9c2 cells using RT-qPCR, Western blot, and ELISA. The role of 20-HETE in Ang II-induced cardiac hypertrophy was examined using DHE, MitoSOX, and JC-1 staining to evaluate reactive oxygen species (ROS) generation and mitochondrial membrane potential changes. The ERK/Akt and CaN/NFAT3 signaling pathways were analyzed through Western blot. Ang II was found to promote CYP4A expression and 20-HETE production in H9c2 cells via an AT1 receptor-dependent mechanism. Additionally, the upregulation of AT1 receptor expression by 20-HETE further confirms its facilitatory effect on the Ang II signaling pathway. Inhibition of 20-HETE synthesis or blockade of its receptor, G-protein-coupled receptor 75 (GPR75), significantly reversed Ang II-induced cardiac hypertrophy. This reversal was closely associated with 20-HETE-induced ROS production, oxidative stress, and activation of the Ca2+/CaN/NFAT3 signaling pathway. This study demonstrated that 20-HETE mediated Ang II-induced cardiac hypertrophy and, for the first time, highlighted the significant role of the GPR75 receptor in this process. These findings suggested that targeting 20-HETE reduction or blocking its receptor action could offer a novel therapeutic approach for cardiovascular diseases associated with Ang II.https://doi.org/10.1038/s41598-025-85992-220-Hydroxyeicosatetraenoic acidAngiotensin IIG protein-coupled receptor 75Cardiac hypertrophyReactive oxygen species |
| spellingShingle | Jingyi Han Jiaojiao Li Lianlian Liu Kaiyuan Li Chun Zhang Yong Han 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells Scientific Reports 20-Hydroxyeicosatetraenoic acid Angiotensin II G protein-coupled receptor 75 Cardiac hypertrophy Reactive oxygen species |
| title | 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells |
| title_full | 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells |
| title_fullStr | 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells |
| title_full_unstemmed | 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells |
| title_short | 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and Ca2+ signaling in H9c2 cells |
| title_sort | 20 hete mediates ang ii induced cardiac hypertrophy via ros and ca2 signaling in h9c2 cells |
| topic | 20-Hydroxyeicosatetraenoic acid Angiotensin II G protein-coupled receptor 75 Cardiac hypertrophy Reactive oxygen species |
| url | https://doi.org/10.1038/s41598-025-85992-2 |
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