biostudies-literatureLing QBeijing Nova ProgramNational Natural Science Foundation of China1400-1415https://www.ebi.ac.uk/biostudies/studies/S-EPMC12464868biostudies-literatureUnknown8(8)<h4>Background</h4>SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear.<h4>Methods</h4>In vascular smooth muscle cells (VSMCs), we employed gain- and loss-of-function approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2 (AAV2) to validate the findings in vivo.<h4>Results</h4>We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin II. Conversely, in vivo overexpression of Sox6 led to a significant elevatiAnimal models and experimental medicineSOX6 enhances vascular smooth muscle cell phenotypic switching and elevates blood pressure by activating autophagy.PMC124648682023048484282470461Huang CDong XCong LChen ZZhang HCai JLing QMao LfalseSOX6 enhances vascular smooth muscle cell phenotypic switching and elevates blood pressure by activating autophagy.<h4>Background</h4>SOX6 has been shown to play a crucial role in the development of the cardiovascular system. However, its potential role in hypertension and vascular function remains unclear.<h4>Methods</h4>In vascular smooth muscle cells (VSMCs), we employed gain- and loss-of-function approaches combined with RNA sequencing, autophagy flux assessment, and phenotype characterization. Additionally, we established a mouse model with Sox6 overexpression via adeno-associated virus 2 (AAV2) to validate the findings in vivo.<h4>Results</h4>We validated the increased expression of SOX6 in hypertension both in vitro and in vivo. Genetic silencing of Sox6 in VSMCs attenuated the phenotypic switching induced by angiotensin II. Conversely, in vivo overexpression of Sox6 led to a significant elevati2025-01-01T00:00:00Z2025 Aug2026-06-03T21:21:56.575Z2026-05-01T03:10:57.867ZS-EPMC124648684050140810.1002/ame2.70046