Jue-Yu Zhang1, Luo Lei1, Jun Shang1, Tian-Ming Huo1, Bo Zhang1, Gang Chen2, Zhi-Yu Zeng3, Shi-Kang Li4. 1. Department of Thoracic and Cardiovascular Diseases, First Affiliated Hospital of Guangxi Medical University, Nanning, China. 2. Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, China. 3. Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: zhiyuzeng@163.com. 4. Department of Thoracic and Cardiovascular Diseases, First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: shikangli@hotmail.com.
Abstract
BACKGROUND: Neointimal hyperplasia, which is caused by dysfunction of vascular smooth muscle cells and vascular endothelial cells (VECs), is a foundation for later development of vein grafted occlusion. This study investigates whether neointimal hyperplasia could be prevented by the application of paeonol, a phenolic compound having functions of anti-inflammatory, anti-oxidant, and anti-proliferative. METHODS: Autologous jugular veins, which engrafted to carotid arteries in rabbits, were enveloped with paeonol or left untreated. After 0, 2, and 3 wk, vein grafts were respectively harvested. Proliferating cell nuclear antigen, vascular cell adhesion molecule l (VCAM-1), and intercellular cell adhesion molecule 1 were assessed with immunohistochemistry and Western blot. VECs apoptosis was also detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. RESULTS: Paeonol treatment reduced early neointimal hyperplasia by 42%-46% (P < 0.001) and early medial hyperplasia by 18%-22% (P < 0.001) compared with the controls. Immunohistochemical and Western blot results show a significant downregulation of proliferating cell nuclear antigen (P < 0.001) and VCAM-1 (P < 0.001) in paeonol treatment group in the second and third weeks. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling analysis discovered that VECs apoptosis was also reduced by the paeonol treatment in the second and third weeks (P < 0.001). CONCLUSIONS: Paeonol could prevent vein graft early restenosis by suppressing intimal and medial hyperplasia via inhibition of vascular smooth muscle cells proliferation, VCAM-1 expression, and anti-apoptosis of VECs in grafted veins.
BACKGROUND: Neointimal hyperplasia, which is caused by dysfunction of vascular smooth muscle cells and vascular endothelial cells (VECs), is a foundation for later development of vein grafted occlusion. This study investigates whether neointimal hyperplasia could be prevented by the application of paeonol, a phenolic compound having functions of anti-inflammatory, anti-oxidant, and anti-proliferative. METHODS: Autologous jugular veins, which engrafted to carotid arteries in rabbits, were enveloped with paeonol or left untreated. After 0, 2, and 3 wk, vein grafts were respectively harvested. Proliferating cell nuclear antigen, vascular cell adhesion molecule l (VCAM-1), and intercellular cell adhesion molecule 1 were assessed with immunohistochemistry and Western blot. VECs apoptosis was also detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling assay. RESULTS:Paeonol treatment reduced early neointimal hyperplasia by 42%-46% (P < 0.001) and early medial hyperplasia by 18%-22% (P < 0.001) compared with the controls. Immunohistochemical and Western blot results show a significant downregulation of proliferating cell nuclear antigen (P < 0.001) and VCAM-1 (P < 0.001) in paeonol treatment group in the second and third weeks. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling analysis discovered that VECs apoptosis was also reduced by the paeonol treatment in the second and third weeks (P < 0.001). CONCLUSIONS:Paeonol could prevent vein graft early restenosis by suppressing intimal and medial hyperplasia via inhibition of vascular smooth muscle cells proliferation, VCAM-1 expression, and anti-apoptosis of VECs in grafted veins.