Background : 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. Methods : In vascular smooth ...Background : 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. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction 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. Results : 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 elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.展开更多
基金Beijing Nova Program,Grant/Award Number:20230484842National Natural Science Foundation of China,Grant/Award Number:82470461。
文摘Background : 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. Methods : In vascular smooth muscle cells(VSMCs), we employed gain-and loss-offunction 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. Results : 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 elevation in blood pressure and promoted vascular remodeling. Mechanistically, SOX6 was shown to regulate phenotypic switching via an autophagydependent pathway. Specifically, Sox6 overexpression augmented VSMC autophagy and facilitated phenotypic switching, whereas Sox6 knockdown yielded opposite outcomes. Modulation of autophagy using 3-MA or RAPA could effectively counteract the effect mediated by SOX6. Conclusions : Our findings revealed that SOX6 regulates VSMC plasticity and elevates blood pressure by activating autophagy. Therefore, SOX6 inhibition potentially represents a novel strategy for treating hypertension and vascular remodeling.
