Abstract
Hypertension is a clinical syndrome characterized by increased systemic arterial blood pressure, affecting about 1.4 billion people currently worldwide with only one in seven cases adequately controlled. It is the main contributing factor of cardiovascular diseases (CVDs), often co-existing with other CVDs risk factors to impair the structure and function of important organs such as heart, brain, and kidney, and ultimately lead to multi-organ failure. Vascular remodeling is a critical process in the development of essential hypertension, and phenotype switching of vascular smooth muscle cells (VSMCs) was reported contributing substantially to vascular remodeling. circHIPK2 is a circular RNA (circRNA) derived from the second exon of homeodomain-interacting protein kinase 2 (HIPK2). Several studies revealed that circHIPK2 functions in various diseases by serving as a microRNA (miRNA) sponge. However, the functional roles and molecular mechanisms of circHIPK2 in VSMC phenotype switching and hypertension are not clear. In the present study, we showed that the expression of circHIPK2 was significantly upregulated in the VSMCs of hypertensive patients. Functional studies showed that circHIPK2 promoted the Angiotensin II (AngII)-induced VSMC phenotype switching by acting as the sponge of miR-145-5p, thereby upregulating the expression of a disintegrin and metalloprotease (ADAM) 17. Collectively, our study provides a new therapeutic target for hypertension.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
We thank Professor Yufeng Zhou from Children’s Hospital of Fudan University for technical assistance.
Funding
This research is supported by Grant No. 2018YFC2002400 from the National Key R&D Program of China.
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CL, NL, FL, WD, GD, YT, and YZ designed and carried out experiments, and analyzed the data. HF recruited the human participants. CL and HF wrote the manuscript. HF and JJ planned, designed, supervised, and coordinated the overall research efforts.
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The human subjects were recruited from the Tongji Hospital of Tongji University. Written informed consent was obtained from all participating subjects. Human Experiments was approved by the Ethics Committee of Shanghai Tongji Hospital.
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Liu, C., Li, N., Li, F. et al. CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension. J Hum Hypertens 37, 1021–1027 (2023). https://doi.org/10.1038/s41371-023-00834-w
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DOI: https://doi.org/10.1038/s41371-023-00834-w
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