2. Academic Validation
  3. Endothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice

Endothelial Sp1/Sp3 are essential to the effect of captopril on blood pressure in male mice

  • Nat Commun. 2023 Sep 21;14(1):5891. doi: 10.1038/s41467-023-41567-1.
Hanlin Lu # 1,  Xiuxin Jiang # 2,  Lifan He 1,  Xuyang Ji 1,  Xinyun Li 1,  Shaozhuang Liu 2,  Yuanyuan Sun 1,  Xiaoteng Qin 1,  Xiwen Xiong 3,  Sjaak Philipsen 4,  Bo Xi 5,  Meng Zhang 1,  Jianmin Yang 1,  Cheng Zhang 1,  Yun Zhang 1,  Wencheng Zhang 6
Affiliations

Affiliations

  • 1 National Key Laboratory for Innovation and Transformation of Luobing Theory; The 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, China.
  • 2 Department of Bariatric and Metabolic Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 3 School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan, China.
  • 4 Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
  • 5 Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 6 National Key Laboratory for Innovation and Transformation of Luobing Theory; The 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, China. [email protected].
  • # Contributed equally.
PMID: 37735515 DOI: 10.1038/s41467-023-41567-1
Abstract

Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting Enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells. Tamoxifen-induced deletion of endothelial Sp1 and Sp3 in male mice decreases the serum nitrite/nitrate level, impairs endothelium-dependent vasodilation, and causes hypertension and cardiac remodeling. The beneficial actions of captopril are abolished by endothelial-specific deletion of Sp1/Sp3, indicating that they may be targets for ACEIs. Captopril increases Sp1/Sp3 protein levels by recruiting histone deacetylase 1, which elevates deacetylation and suppressed degradation of Sp1/Sp3. Sp1/Sp3 represents innovative therapeutic target for captopril to prevent cardiovascular diseases.

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