CircHIPK2 facilitates phenotypic switching of vascular smooth muscle cells in hypertension.

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.