Curcumin Regulates VSMC Phenotype Transition via Modulation of Notch and Wnt Signaling Pathways

Abstract

Abstract Preclinical Research In the development of cardiovascular diseases, vascular smooth muscle cells (VSMCs) undergo transition from a contractile to a synthetic phenotype. Notch‐ and Wnt‐dependent signaling pathways play a critical role during this process. Curcumin has potential for clinical use including anti‐inflammatory and antitumor actions. However, the effect of curcumin on VSMC phenotype transition remains unclear. In VSMCs isolated from the thoracic aorta of Sprague Dawley rats, curcumin (5–20 μM) produced a concentration‐dependent inhibition of serum‐elicited VSMC migration. Furthermore, curcumin, at the dose of 20 μM, partially reversed the repression of VSMC markers induced by serum stimulation, an effect associated with attenuation of Jagged‐1 and Notch‐1 levels and downregulation of the downstream gene Hey‐1. Downregulation of Wnt‐4 was also observed after curcumin treatment in the presence of serum, which was followed by inhibition of nuclear β‐catenin translocation and cyclin D1 expression. These data suggest that curcumin is a potent regulator of VSMCs phenotype transition and may play a critical role in regulating these events after vascular injury.