Paeonol Suppresses Vasculogenesis Through Regulating Vascular Smooth Muscle Phenotypic Switching

Abstract

Objective: Smooth muscle cell (SMC) phenotypic switching is associated with development of a variety of occlusive vascular diseases. Paeonol has been reported to be involved in suppressing SMC proliferation. However, it is still unknown whether paeonol can regulate SMC phenotypic switching, and which eventually result in suppressing vasculogenesis. Methods: Murine left common carotid artery was injured by completely ligation, and paeonol was administrated by intraperitoneal injection. Hematoxylin and eosin (H&E) staining was performed to visualize vascular neointima formation. Rat aortic SMCs were used to determine whether paeonol suppresses cell proliferation and migration. And murine hind limb ischemia model was performed to confirm the function role of paeonol in suppressing vasculogenesis. Results: Complete ligation of murine common carotid artery successfully induced neointima formation. Paeonol treatment dramatically reduced the size of injury-induced neointima. Using rat aortic primary SMC, we identified that paeonol strongly suppressed cell proliferation, migration, and decreased extracellular matrix deposition. And paeonol treatment dramatically suppressed vasculogenesis after hind limb ischemia injury. Conclusion: Paeonol could regulate SMC phenotypic switching through inhibiting proliferation and migration of SMC, which results in inhibiting ischemia-induced vasculogenesis.

Paeonol Promotes Reendothelialization After Vascular Injury Through Activation of c-Myc/VEGFR2 Signaling Pathway

“…Based on our previous studies of Paeonol regulated pathological vascular remodeling by monitoring vascular smooth muscle cell phenotypic switching, 26 we hypothesized that Paeonol may contribute to reendothelialization, which is involved in pathological vascular remodeling. We treated HUVEC with Paeonol and performed Real-Time PCR to evaluate vasculogenic signaling pathways.…”

“…Paeonol is a natural ingredient isolated from Paeonia Suffruticosa and Paeonol lactiflora pall. 26 Our previous studies have demonstrated that Paeonol suppresses SMC phenotypic switching associated with neointima formation by inhibiting SMC proliferation and mobility. However, whether inhibition of neointima formation is due to regulating reendothelialization is unknown.…”

Andrographolide suppresses hypoxia-induced embryonic hyaloid vascular system development through HIF-1a/VEGFR2 signaling pathway

“…For IHC staining, the slides were deparaffinized and antigen retrieval was performed with citric acid treatment at 98°C for 5 to10 min. After antigenic unmasking, the slides were incubated with CD31 (Cell Signaling Technology, 1:200) ( 34 ), HIF-1α (Cell Signaling Technology, 1:200) ( 35 ), and VRGF Receptor 2 (Cell Signaling Technology, 1:200) ( 36 ) overnight at 4°C. This was followed by incubation with biotinylated secondary antibodies at room temperature for 1 h (Vector Laboratories), and incubation in ABC solution (Vector Laboratories) for 30 min at room temperature.…”

Protective mechanism of Paeonol on central nervous system

“…Its research indicates that Pae's anti‐myocardial fibrosis effect is related to this pathway (Chen, Zhang, et al, 2022). Pae reduces the possibility of pathological angiogenesis by inhibiting the proliferation and migration of smooth muscle cells (Xu et al, 2022). Similarly, Shi et al (2022) found that Pae inhibited the increase of lipopolysaccharides (LPS) to improve the disorder of intestinal flora and inhibited the proliferation of vascular smooth muscle cells to improve atherosclerosis.…”