The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II
Inflammation induced by angiotensin II (Ang II) is a key event in the progression of numerous cardiovascular diseases. Astragaloside IV (AS-IV), a glycoside extracted from Astragalus membranaceus Bunge, has been shown to inhibit Ang II–induced inflammatory responses in vivo. However, the mechanisms...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2024/3193950 |
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| author | Shiyu Zhang Shijie Li Shiyang Xie Lin Cui Yuan Gao Youping Wang |
| author_facet | Shiyu Zhang Shijie Li Shiyang Xie Lin Cui Yuan Gao Youping Wang |
| author_sort | Shiyu Zhang |
| collection | DOAJ |
| description | Inflammation induced by angiotensin II (Ang II) is a key event in the progression of numerous cardiovascular diseases. Astragaloside IV (AS-IV), a glycoside extracted from Astragalus membranaceus Bunge, has been shown to inhibit Ang II–induced inflammatory responses in vivo. However, the mechanisms underlying the beneficial effects are still unclear. This study investigated whether AS-IV attenuates endothelial inflammation induced by Ang II via the activation of endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Human umbilical vein endothelial cells (HUVECs) were cultured in the presence of AS-IV with or without the specific inhibitor of NOS or Ca2+- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent cascade prior to Ang II exposure. Incubation of HUVECs with AS-IV enhanced NO production and eNOSser1177 phosphorylation. These responses were abrogated by the inhibition of NOS or Ca2+- and PI3K/Akt-dependent pathway. In addition, preincubation of HUVECs with AS-IV inhibited Ang II–induced cytokine and chemokine production, adhesion molecule expression, monocyte adhesion, and nuclear factor kappa B (NF-κB) activation as evidenced by the attenuation of inhibitor of kappa B alpha phosphorylation and subsequent NF-κB DNA binding. These effects of AS-IV were abolished by the suppression of NOS or Ca2+- and PI3K/Akt-dependent cascade. Our findings indicate that AS-IV attenuates inflammatory responses triggered by Ang II possibly via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway in endothelial cells. |
| format | Article |
| id | doaj-art-cf24af71a16043e9a5ff45fcd3bebf24 |
| institution | DOAJ |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
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| series | Mediators of Inflammation |
| spelling | doaj-art-cf24af71a16043e9a5ff45fcd3bebf242025-08-20T03:06:04ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/3193950The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin IIShiyu Zhang0Shijie Li1Shiyang Xie2Lin Cui3Yuan Gao4Youping Wang5Division of Cardiology and Central LaboratoryDivision of Cardiology and Central LaboratoryDivision of Cardiology and Central LaboratoryDivision of Cardiology and Central LaboratoryDivision of Cardiology and Central LaboratoryDivision of Cardiology and Central LaboratoryInflammation induced by angiotensin II (Ang II) is a key event in the progression of numerous cardiovascular diseases. Astragaloside IV (AS-IV), a glycoside extracted from Astragalus membranaceus Bunge, has been shown to inhibit Ang II–induced inflammatory responses in vivo. However, the mechanisms underlying the beneficial effects are still unclear. This study investigated whether AS-IV attenuates endothelial inflammation induced by Ang II via the activation of endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Human umbilical vein endothelial cells (HUVECs) were cultured in the presence of AS-IV with or without the specific inhibitor of NOS or Ca2+- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent cascade prior to Ang II exposure. Incubation of HUVECs with AS-IV enhanced NO production and eNOSser1177 phosphorylation. These responses were abrogated by the inhibition of NOS or Ca2+- and PI3K/Akt-dependent pathway. In addition, preincubation of HUVECs with AS-IV inhibited Ang II–induced cytokine and chemokine production, adhesion molecule expression, monocyte adhesion, and nuclear factor kappa B (NF-κB) activation as evidenced by the attenuation of inhibitor of kappa B alpha phosphorylation and subsequent NF-κB DNA binding. These effects of AS-IV were abolished by the suppression of NOS or Ca2+- and PI3K/Akt-dependent cascade. Our findings indicate that AS-IV attenuates inflammatory responses triggered by Ang II possibly via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway in endothelial cells.http://dx.doi.org/10.1155/2024/3193950 |
| spellingShingle | Shiyu Zhang Shijie Li Shiyang Xie Lin Cui Yuan Gao Youping Wang The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II Mediators of Inflammation |
| title | The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II |
| title_full | The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II |
| title_fullStr | The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II |
| title_full_unstemmed | The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II |
| title_short | The Role of Ca2+/PI3K/Akt/eNOS/NO Pathway in Astragaloside IV–Induced Inhibition of Endothelial Inflammation Triggered by Angiotensin II |
| title_sort | role of ca2 pi3k akt enos no pathway in astragaloside iv induced inhibition of endothelial inflammation triggered by angiotensin ii |
| url | http://dx.doi.org/10.1155/2024/3193950 |
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