title: Astragaloside IV protects against cardiac hypertrophy via inhibiting the Ca2+/CaN signaling pathway.
abstract: Astragaloside IV is widely used for the treatment of cardiovascular diseases in China. However, its role in cardiac hypertrophy remains unclear. In this study, we aim to determine the protective effects of astragaloside IV on myocardial hypertrophy induced by lipopolysaccharide and to identify their precise molecular and cellular mechanisms. Cell size, reorganization of actin filaments, and ANP and BNP mRNA expression were used as indices of hypertrophy; CaN and GATA-4 expression and the distribution of NFAT-3 in both cytoplasm and nucleus were determined by Western blot analysis; Ca2+ transient in Fura-2/AM-loaded cells was measured by Till image system. Our data demonstrated that lipopolysaccharide challenge induced cardiac hypertrophy, increased resting Ca2+ transient level, promoted activation of CaN and GATA-4, and enhanced nuclear translocation of NFAT-3. Administration of astragaloside IV (16, 32, and 64 µM) 1 h prior to lipopolysaccharide stimulation dose-dependently attenuated cardiac hypertrophy induced by lipopolysaccharide. Further studies demonstrated that astragaloside IV inhibited the increment of the resting intracellular free Ca2+, and its effect was similar to verapamil. Moreover, astragaloside IV also inhibited the activation of CaN and GATA-4, and the nuclear translocation of NFAT-3 induced by lipopolysaccharide. In conclusion, our results revealed that astragaloside IV had the potential to protect against cardiac hypertrophy through Ca2+-mediated CaN signaling pathways.
authors: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China.
authors: Meili
authors: M
authors: Lu
authors: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China.
authors: Hongxin
authors: H
authors: Wang
authors: First Affiliated Hospital of Liaoning Medical University, Jinzhou, China.
authors: Jing
authors: J
authors: Wang
authors: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China.
authors: Jing
authors: J
authors: Zhang
authors: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China.
authors: Juan
authors: J
authors: Yang
authors: Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, China.
authors: Lingjun
authors: L
authors: Liang
authors: Laboratory of Experimental Cardiology, Institute of Cardiology, Tomsk, Russia.
authors: Leonid N
authors: LN
authors: Maslov
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D019703:Calcineurin / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; D012503:Saponins; D014315:Triterpenes; D020097:Natriuretic Peptide, Brain; C052064:astragaloside A; D009320:Atrial Natriuretic Factor; D019703:Calcineurin