Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway
ObjectiveTo investigate the protective effect and mechanism of quercetin (QR) against angiotensin Ⅱ (Ang Ⅱ)-induced injury and phenotypic transformation in vascular smooth muscle cells (VSMCs). MethodsVSMCs were treated with Ang Ⅱ and divided into four groups: control (Ctrl), QR control, model (Ang...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Shanghai Chinese Clinical Medicine Press Co., Ltd.
2025-08-01
|
| Series: | Zhongguo Linchuang Yixue |
| Subjects: | |
| Online Access: | https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250453 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849223007619252224 |
|---|---|
| author | Mamatimin ABDURESHIT Wei ZHU |
| author_facet | Mamatimin ABDURESHIT Wei ZHU |
| author_sort | Mamatimin ABDURESHIT |
| collection | DOAJ |
| description | ObjectiveTo investigate the protective effect and mechanism of quercetin (QR) against angiotensin Ⅱ (Ang Ⅱ)-induced injury and phenotypic transformation in vascular smooth muscle cells (VSMCs). MethodsVSMCs were treated with Ang Ⅱ and divided into four groups: control (Ctrl), QR control, model (Ang Ⅱ), and treatment (Ang Ⅱ＋QR) groups. Intracellular reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were measured. Western blotting was used to assess protein expression related to inflammation, apoptosis, extracellular matrix (ECM) remodeling, phenotypic transformation, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify mRNA levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]). Cell migration was evaluated using a scratch assay. A rescue experiment employing the Nrf2 transcriptional activity inhibitor ML385 was conducted to further validate protective mechanism of QR for VSMCs. ResultsCompared to the Ctrl group, Ang Ⅱ-treated VSMCs exhibited significantly higher ROS levels, suppressed SOD activity, upregulated expression of inflammatory proteins and mRNA (IL-1β, IL-6, TNF-α), increased matrix metalloproteinase (MMP) protein expression (P＜0.05), enhanced migration capacity, reduced expression of contractile phenotype markers (smooth muscle 22 alpha [SM22α] and α-smooth muscle actin [α-SMA]), upregulated expression of the synthetic phenotype marker osteopontin (OPN), and significantly increased apoptosis (P＜0.05). QR intervention significantly reduced intracellular ROS level, increased SOD activity, decreased protein expression of vascular cell adhesion molecule-1 (VCAM-1) and phosphorylated nuclear factor-κB (NF-κB), downregulated inflammatory cytokine transcription, upregulated contractile phenotype marker expression, and attenuated apoptosis and migration capacity (P＜0.05). The rescue experiment confirmed that QR alleviated Ang Ⅱ-induced oxidative stress, inflammation-related injury, and suppressed the transition of VSMCs towards a synthetic phenotype via activation of Nrf2. Conclusions QR mitigates Ang Ⅱ-induced oxidative stress, inflammation, and apoptosis in VSMCs, inhibits ECM remodeling and VSMCs migration, and consequently suppresses VSMCs phenotypic transformation, primarily through promoting Nrf2 expression. |
| format | Article |
| id | doaj-art-e66f086bffd9424c9544f7d3258a95dd |
| institution | Kabale University |
| issn | 1008-6358 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Shanghai Chinese Clinical Medicine Press Co., Ltd. |
| record_format | Article |
| series | Zhongguo Linchuang Yixue |
| spelling | doaj-art-e66f086bffd9424c9544f7d3258a95dd2025-08-26T01:29:39ZengShanghai Chinese Clinical Medicine Press Co., Ltd.Zhongguo Linchuang Yixue1008-63582025-08-0132459360310.12025/j.issn.1008-6358.2025.2025045320250453Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathwayMamatimin ABDURESHIT0Wei ZHU1Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaObjectiveTo investigate the protective effect and mechanism of quercetin (QR) against angiotensin Ⅱ (Ang Ⅱ)-induced injury and phenotypic transformation in vascular smooth muscle cells (VSMCs). MethodsVSMCs were treated with Ang Ⅱ and divided into four groups: control (Ctrl), QR control, model (Ang Ⅱ), and treatment (Ang Ⅱ＋QR) groups. Intracellular reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were measured. Western blotting was used to assess protein expression related to inflammation, apoptosis, extracellular matrix (ECM) remodeling, phenotypic transformation, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify mRNA levels of inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α [TNF-α]). Cell migration was evaluated using a scratch assay. A rescue experiment employing the Nrf2 transcriptional activity inhibitor ML385 was conducted to further validate protective mechanism of QR for VSMCs. ResultsCompared to the Ctrl group, Ang Ⅱ-treated VSMCs exhibited significantly higher ROS levels, suppressed SOD activity, upregulated expression of inflammatory proteins and mRNA (IL-1β, IL-6, TNF-α), increased matrix metalloproteinase (MMP) protein expression (P＜0.05), enhanced migration capacity, reduced expression of contractile phenotype markers (smooth muscle 22 alpha [SM22α] and α-smooth muscle actin [α-SMA]), upregulated expression of the synthetic phenotype marker osteopontin (OPN), and significantly increased apoptosis (P＜0.05). QR intervention significantly reduced intracellular ROS level, increased SOD activity, decreased protein expression of vascular cell adhesion molecule-1 (VCAM-1) and phosphorylated nuclear factor-κB (NF-κB), downregulated inflammatory cytokine transcription, upregulated contractile phenotype marker expression, and attenuated apoptosis and migration capacity (P＜0.05). The rescue experiment confirmed that QR alleviated Ang Ⅱ-induced oxidative stress, inflammation-related injury, and suppressed the transition of VSMCs towards a synthetic phenotype via activation of Nrf2. Conclusions QR mitigates Ang Ⅱ-induced oxidative stress, inflammation, and apoptosis in VSMCs, inhibits ECM remodeling and VSMCs migration, and consequently suppresses VSMCs phenotypic transformation, primarily through promoting Nrf2 expression.https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250453quercetinintracranial aneurysmvascular smooth muscle celloxidative stressphenotypic transformationnuclearfactor erythroid 2-related factor 2 |
| spellingShingle | Mamatimin ABDURESHIT Wei ZHU Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway Zhongguo Linchuang Yixue quercetin intracranial aneurysm vascular smooth muscle cell oxidative stress phenotypic transformation nuclearfactor erythroid 2-related factor 2 |
| title | Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway |
| title_full | Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway |
| title_fullStr | Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway |
| title_full_unstemmed | Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway |
| title_short | Quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin Ⅱ through Nrf2/HO-1 signaling pathway |
| title_sort | quercetin regulates phenotypic transformation of vascular smooth muscle cells induced by angiotensin ii through nrf2 ho 1 signaling pathway |
| topic | quercetin intracranial aneurysm vascular smooth muscle cell oxidative stress phenotypic transformation nuclearfactor erythroid 2-related factor 2 |
| url | https://www.c-jcm.com/article/doi/10.12025/j.issn.1008-6358.2025.20250453 |
| work_keys_str_mv | AT mamatiminabdureshit quercetinregulatesphenotypictransformationofvascularsmoothmusclecellsinducedbyangiotensiniithroughnrf2ho1signalingpathway AT weizhu quercetinregulatesphenotypictransformationofvascularsmoothmusclecellsinducedbyangiotensiniithroughnrf2ho1signalingpathway |