Wen-Lin Liu1, Qiang Liu2. 1. Affiliated Hospital of Guangdong Medical University; Clinical Research Center of Affiliated Hospital of Guangdong Medical University. 2. Affiliated Hospital of Guangdong Medical University; Clinical Research Center of Affiliated Hospital of Guangdong Medical University. Electronic address: liuqiangmd1@yeah.net.
Abstract
AIMS: Shikonin is a naphthoquinone compound extracted from the root of Lithospermum with various pharmacological activities. Sympathetic neural remodeling greatly contributes to chronic heart failure. Growing evidence has identified a critical role of microRNAs (miRNAs) in a variety of cardiac biological processes. This study aimed to verify whether shikonin could attenuate sympathetic neural remodeling and explore the possible regulatory role of miRNAs in this process. MAIN METHODS: Shikonin was administered to mice after transverse aortic constriction (TAC). Immunohistochemistry and western blotting were used to assess the expression of TAC-induced sympathetic remodeling-related proteins. KEY FINDINGS: TAC-induced expression of the sympathetic remodeling-related proteins, tyrosine hydroxylase (TH), growth associated protein 43 (GAP43), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and nerve growth factor (NGF), was significantly decreased in cardiac tissues. MiR-124 expression significantly increased after heart failure and decreased after shikonin treatment. An adeno-associated virus 9 (AAV9) vector was packaged and used to transfect myocardial tissues of aortic-constricted mice with miR-124, resulting in increased heart miR-124 levels and inhibition of the effects of shikonin on sympathetic neural remodeling. Immunohistochemical staining showed that the density of TH-, GAP43-, and ChAT-positive nerves was significantly increased in aortic-constricted mice after transfection with AAV9-miR-124. SIGNIFICANCE: Our data demonstrate that shikonin administration prevents sympathetic neural remodeling in mice with TAC-induced heart failure. The effects of shikonin on heart failure may be partly due to miR-124-mediated attenuation of sympathetic remodeling. Our results reveal a novel mechanism underlying the therapeutic effect of shikonin in heart failure.
AIMS: Shikonin is a naphthoquinone compound extracted from the root of Lithospermum with various pharmacological activities. Sympathetic neural remodeling greatly contributes to chronic heart failure. Growing evidence has identified a critical role of microRNAs (miRNAs) in a variety of cardiac biological processes. This study aimed to verify whether shikonin could attenuate sympathetic neural remodeling and explore the possible regulatory role of miRNAs in this process. MAIN METHODS: Shikonin was administered to mice after transverse aortic constriction (TAC). Immunohistochemistry and western blotting were used to assess the expression of TAC-induced sympathetic remodeling-related proteins. KEY FINDINGS: TAC-induced expression of the sympathetic remodeling-related proteins, tyrosine hydroxylase (TH), growth associated protein 43 (GAP43), choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT), and nerve growth factor (NGF), was significantly decreased in cardiac tissues. MiR-124 expression significantly increased after heart failure and decreased after shikonin treatment. An adeno-associated virus 9 (AAV9) vector was packaged and used to transfect myocardial tissues of aortic-constricted mice with miR-124, resulting in increased heart miR-124 levels and inhibition of the effects of shikonin on sympathetic neural remodeling. Immunohistochemical staining showed that the density of TH-, GAP43-, and ChAT-positive nerves was significantly increased in aortic-constricted mice after transfection with AAV9-miR-124. SIGNIFICANCE: Our data demonstrate that shikonin administration prevents sympathetic neural remodeling in mice with TAC-induced heart failure. The effects of shikonin on heart failure may be partly due to miR-124-mediated attenuation of sympathetic remodeling. Our results reveal a novel mechanism underlying the therapeutic effect of shikonin in heart failure.