Dehydrocorydaline maintains the vascular smooth muscle cell contractile phenotype by upregulating Spta1

Vascular smooth muscle cell (VSMC) phenotypic switching plays a crucial role in the initiation and progression of atherosclerosis. Dehydrocorydaline (DHC), a major active component of the traditional Chinese herbal medicine Rhizoma Corydalis, exhibits diverse pharmacological effects. However, its impact on VSMCs remains largely unknown. This study aims to investigate the effects and underlying mechanisms of DHC in phenotypic switching of VSMCs. Our study revealed that DHC increased the mRNA and protein levels of rat VSMC contractile phenotype markers, such as calponin 1 (Cnn1), myosin heavy chain (Myh11, SM-MHC), smooth muscle 22α (Sm22α), and alpha-smooth muscle actin (Acta2, α-SMA) in a time- and dose-dependent manner. Additionally, DHC inhibited platelet-derived growth factor-BB-induced VSMC proliferation and migration. In Apoe^-/- mice, DHC treatment resulted in reduced carotid plaque areas and macrophage infiltration, along with increased contractile phenotype marker expression. RNA sequencing analysis revealed a significant upregulation of spectrin alpha, erythrocytic 1 (Spta1) in DHC-treated rat VSMCs. Strikingly, Spta1 knockdown effectively negated the increase in contractile phenotype marker expression in VSMCs that was initially prompted by DHC. Therefore, DHC preserves the VSMC contractile phenotype through Spta1, thereby attenuating carotid artery atherosclerotic plaques in Apoe^-/- mice. This study provides evidence supporting the potential use of Chinese herbal medicines, particularly those containing DHC such as Rhizoma Corydalis, in the treatment of atherosclerotic cardiovascular disease, thus expanding the clinical application of such herbal remedies.