Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure

Zhenguo Wang; Wenjuan Mu; Juan Zhong; Ruiyan Xu; Yaozhong Liu; Guizhen Zhao; Yanhong Guo; Jifeng Zhang; Ida Surakka; Y. Eugene Chen; Lin Chang

doi:10.1172/JCI183409

¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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¹Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, United States of America

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J Clin Invest. https://doi.org/10.1172/JCI183409.
Copyright © 2024, Wang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published December 3, 2024 - Version history

Disruptions of blood pressure (BP) circadian variation are closely associated with an increased risk of cardiovascular disease (CVD). Thus, gaining insights into the molecular mechanisms of BP circadian variation is essential for comprehending BP regulation. Human genetic analyses suggest that PR domain-containing protein 16 (PRDM16), a transcription factor highly expressed in vascular smooth muscle cells (VSMC), is significantly associated with BP-related traits. However, the roles of PRDM16 in BP regulation are largely unknown. Here, we demonstrate that BP in VSMC-specific Prdm16 knockout (Prdm16^SMKO) mice was significantly lower than that in control mice during the active period, resulting in aberrant BP circadian variation. Mesenteric artery rings from Prdm16^SMKO mice showed reduced response to phenylephrine. Mechanistically, we identified adrenergic receptor alpha 1d (Adra1d) as a transcriptional target of PRDM16. Notably, PRDM16 exhibits a remarkable circadian expression pattern and regulates the expression of clock genes, particularly Npas2, which is crucial for BP circadian variation regulation. Consequently, PRDM16 deficiency in VSMC causes disrupted BP circadian variation through reduced response to adrenergic signaling and clock gene regulation. Our findings offer substantial insights into the intricate molecular pathways that govern circadian fluctuations in BP.

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Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure

Zhenguo Wang,¹ Wenjuan Mu,¹ Juan Zhong,¹ Ruiyan Xu,¹ Yaozhong Liu,¹ Guizhen Zhao,¹ Yanhong Guo,¹ Jifeng Zhang,¹ Ida Surakka,¹ Y. Eugene Chen,¹ and Lin Chang¹

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Vascular smooth muscle cell PRDM16 regulates circadian variation in blood pressure

Zhenguo Wang,1 Wenjuan Mu,1 Juan Zhong,1 Ruiyan Xu,1 Yaozhong Liu,1 Guizhen Zhao,1 Yanhong Guo,1 Jifeng Zhang,1 Ida Surakka,1 Y. Eugene Chen,1 and Lin Chang1

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Zhenguo Wang,¹ Wenjuan Mu,¹ Juan Zhong,¹ Ruiyan Xu,¹ Yaozhong Liu,¹ Guizhen Zhao,¹ Yanhong Guo,¹ Jifeng Zhang,¹ Ida Surakka,¹ Y. Eugene Chen,¹ and Lin Chang¹