ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure
Abstract Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. Zinc finger protein 36 (ZFP36) is an RNA‐binding protein that regulates mRNA stability by binding to adenylate‐uridylate‐rich elements in the mRNA 3′‐untranslated reg...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408811 |
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| author | Xiuru Cui Yawei Wang Hanlin Lu Lei Wang Xianwei Xie Shenghao Zhang Pavel Kovarik Shuijie Li Shanshan Liu Qunye Zhang Jianmin Yang Cheng Zhang Jinwei Tian Yan Liu Wencheng Zhang |
| author_facet | Xiuru Cui Yawei Wang Hanlin Lu Lei Wang Xianwei Xie Shenghao Zhang Pavel Kovarik Shuijie Li Shanshan Liu Qunye Zhang Jianmin Yang Cheng Zhang Jinwei Tian Yan Liu Wencheng Zhang |
| author_sort | Xiuru Cui |
| collection | DOAJ |
| description | Abstract Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. Zinc finger protein 36 (ZFP36) is an RNA‐binding protein that regulates mRNA stability by binding to adenylate‐uridylate‐rich elements in the mRNA 3′‐untranslated region. This study reveals that ZFP36 expression is highly elevated in the arteries of hypertensive patients and rodents. In cultured vascular smooth muscle cell (VSMC), angiotensin II (AngII) activates poly (ADP‐ribose) polymerases1 (PARP1) to stimulate Zfp36 expression at the transcriptional level. VSMC‐specific ZFP36 deletion reduces vessel contractility and blood pressure levels in mice. Mechanistically, ZFP36 regulates G protein‐coupled receptors (GPCRs)‐mediated increases in intracellular calcium levels through impairing the mRNA stability of regulator of G protein signaling 2 (RGS2). Moreover, the VSMC‐specific ZFP36 deficiency attenuates AngII‐induced hypertension and vascular remodeling in mice. AAV‐mediated ZFP36 knockdown ameliorates spontaneous hypertension in rats. These findings elucidate that ZFP36 plays an important role in the regulation of smooth muscle contraction and blood pressure through modulating RGS2 expression. ZFP36 inhibition may represent a new therapeutic strategy for the treatment of hypertension. |
| format | Article |
| id | doaj-art-f0544ce09cc140adbbe028e130e9edb6 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-f0544ce09cc140adbbe028e130e9edb62025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202408811ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood PressureXiuru Cui0Yawei Wang1Hanlin Lu2Lei Wang3Xianwei Xie4Shenghao Zhang5Pavel Kovarik6Shuijie Li7Shanshan Liu8Qunye Zhang9Jianmin Yang10Cheng Zhang11Jinwei Tian12Yan Liu13Wencheng Zhang14State Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Cardiology Second Affiliated Hospital of Harbin Medical University Heilongjiang Provincial Key Laboratory of Panvascular Disease The Key Laboratory of Myocardial Ischemia Ministry of Education Harbin 150086 ChinaDepartment of Cardiology Second Affiliated Hospital of Harbin Medical University Heilongjiang Provincial Key Laboratory of Panvascular Disease The Key Laboratory of Myocardial Ischemia Ministry of Education Harbin 150086 ChinaMax Perutz Labs University of Vienna Vienna Biocenter (VBC), Dr. Bohr‐Gasse 9 Vienna A‐1030 AustriaDepartment of Biopharmaceutical Sciences College of Pharmacy Harbin Medical University Harbin 150081 ChinaState Key Laboratory of Transvascular Implantation Devices Heart Regeneration and Repair Key Laboratory of Zhejiang Province Department of Cardiology The Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaDepartment of Cardiology Second Affiliated Hospital of Harbin Medical University Heilongjiang Provincial Key Laboratory of Panvascular Disease The Key Laboratory of Myocardial Ischemia Ministry of Education Harbin 150086 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaState Key Laboratory for Innovation and Transformation of Luobing Theory Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education Chinese National Health Commission and Chinese Academy of Medical Sciences Department of Cardiology Qilu Hospital of Shandong University Jinan 250012 ChinaAbstract Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. Zinc finger protein 36 (ZFP36) is an RNA‐binding protein that regulates mRNA stability by binding to adenylate‐uridylate‐rich elements in the mRNA 3′‐untranslated region. This study reveals that ZFP36 expression is highly elevated in the arteries of hypertensive patients and rodents. In cultured vascular smooth muscle cell (VSMC), angiotensin II (AngII) activates poly (ADP‐ribose) polymerases1 (PARP1) to stimulate Zfp36 expression at the transcriptional level. VSMC‐specific ZFP36 deletion reduces vessel contractility and blood pressure levels in mice. Mechanistically, ZFP36 regulates G protein‐coupled receptors (GPCRs)‐mediated increases in intracellular calcium levels through impairing the mRNA stability of regulator of G protein signaling 2 (RGS2). Moreover, the VSMC‐specific ZFP36 deficiency attenuates AngII‐induced hypertension and vascular remodeling in mice. AAV‐mediated ZFP36 knockdown ameliorates spontaneous hypertension in rats. These findings elucidate that ZFP36 plays an important role in the regulation of smooth muscle contraction and blood pressure through modulating RGS2 expression. ZFP36 inhibition may represent a new therapeutic strategy for the treatment of hypertension.https://doi.org/10.1002/advs.202408811blood pressurehypertensionsmooth muscle contractionZFP36 |
| spellingShingle | Xiuru Cui Yawei Wang Hanlin Lu Lei Wang Xianwei Xie Shenghao Zhang Pavel Kovarik Shuijie Li Shanshan Liu Qunye Zhang Jianmin Yang Cheng Zhang Jinwei Tian Yan Liu Wencheng Zhang ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure Advanced Science blood pressure hypertension smooth muscle contraction ZFP36 |
| title | ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure |
| title_full | ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure |
| title_fullStr | ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure |
| title_full_unstemmed | ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure |
| title_short | ZFP36 Regulates Vascular Smooth Muscle Contraction and Maintains Blood Pressure |
| title_sort | zfp36 regulates vascular smooth muscle contraction and maintains blood pressure |
| topic | blood pressure hypertension smooth muscle contraction ZFP36 |
| url | https://doi.org/10.1002/advs.202408811 |
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