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.
Original language | English |
---|---|
Article number | 5891 |
Journal | Nature Communications |
Volume | 14 |
Issue number | 1 |
DOIs | |
Publication status | Published - 21 Sept 2023 |
Bibliographical note
Funding Information:The authors thank Prof. Yulong He from Soochow University for providing the VE-CAD-CreERT2mice. This work was supported by the Natural Science Foundation for Distinguished Young Scholars of Shandong Province (ZR2020JQ30 to W.Z.), the National Natural Science Foundation of China (82270457 to W.Z., 81970198 to W.Z., 81970366 to J.Y., and 82030051 to Y.Z.), the Taishan Scholar Project of Shandong Province of China (tsqn201812131 to M.Z.), and the Shandong Provincial Natural Science Foundation (ZR2020QH024 to X.Q., ZR2020YQ53 to M.Z.).
Funding Information:
The authors thank Prof. Yulong He from Soochow University for providing the VE-CAD-CreER mice. This work was supported by the Natural Science Foundation for Distinguished Young Scholars of Shandong Province (ZR2020JQ30 to W.Z.), the National Natural Science Foundation of China (82270457 to W.Z., 81970198 to W.Z., 81970366 to J.Y., and 82030051 to Y.Z.), the Taishan Scholar Project of Shandong Province of China (tsqn201812131 to M.Z.), and the Shandong Provincial Natural Science Foundation (ZR2020QH024 to X.Q., ZR2020YQ53 to M.Z.). T2
Publisher Copyright:
© 2023, Springer Nature Limited.