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Published on: February 15, 2022
CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension
Chi Liu1,2, Nan Li3, Fangcun Li4
1Emergency Department & National Clinical Research Center for Aging and Medicine, Jing'an District Central Hospital of Shanghai, Fudan University, Shanghai, 200040, China.
Insights
Circular RNA HIPK2 (circHIPK2) promotes hypertension by driving vascular smooth muscle cell changes. Targeting circHIPK2 offers a potential new therapeutic strategy for managing high blood pressure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Genetics
Background:
- Hypertension affects 1.4 billion globally, with poor control rates.
- It is a primary driver of cardiovascular diseases and organ damage.
- Vascular smooth muscle cell (VSMC) phenotype switching is key to hypertension-related vascular remodeling.
Purpose of the Study:
- To investigate the role of circHIPK2 in VSMC phenotype switching and hypertension.
- To elucidate the molecular mechanisms underlying circHIPK2's function in hypertension.
Main Methods:
- Quantitative analysis of circHIPK2 expression in hypertensive patient VSMCs.
- Functional studies on Angiotensin II-induced VSMC phenotype switching.
- Investigation of circHIPK2 as a microRNA (miRNA) sponge for miR-145-5p.
Main Results:
- circHIPK2 expression is significantly increased in VSMCs from hypertensive individuals.
- circHIPK2 promotes Angiotensin II-induced VSMC phenotype switching.
- circHIPK2 acts as a sponge for miR-145-5p, upregulating ADAM17 expression.
Conclusions:
- circHIPK2 plays a critical role in hypertension pathogenesis via VSMC phenotype modulation.
- The circHIPK2/miR-145-5p/ADAM17 axis is a novel mechanism in hypertension.
- circHIPK2 represents a potential therapeutic target for hypertension treatment.
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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