Endothelial-specific deletion of Sp1/Sp3 in male mice abolishes the beneficial effects of captopril on blood pressure and endothelial function, indicating Sp1/Sp3 are essential targets for ACE inhibitors.
Does captopril exert its blood pressure-lowering and endothelial-protective effects via Sp1/Sp3 transcription factors in endothelial cells?
Endothelial Sp1 and Sp3 are essential targets for the blood pressure-lowering and endothelial-protective effects of captopril via AMPKα activation.
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.
Lu et al. (Thu,) conducted a other in Hypertension. Captopril vs. Vehicle / Control mice was evaluated on Blood pressure and endothelial function. Endothelial-specific deletion of Sp1/Sp3 in male mice abolishes the beneficial effects of captopril on blood pressure and endothelial function, indicating Sp1/Sp3 are essential targets for ACE inhibitors.
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