Therapeutic targets of rosuvastatin on heart failure and associated biological mechanisms: A study of network pharmacology and experimental validation.

Autor: Lian Z; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Song JX; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Yu SR; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Su LN; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Cui YX; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Li SF; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Lee CY; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Liang HZ; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China., Chen H; Department of Cardiology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People's Hospital, Beijing, China; Center for Cardiovascular Translational Research, Peking University People's Hospital, Beijing, China. Electronic address: chenhongbj@medmail.com.cn.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2021 Mar 15; Vol. 895, pp. 173888. Date of Electronic Publication: 2021 Jan 22.
DOI: 10.1016/j.ejphar.2021.173888
Abstrakt: To explore the potential targets underlying the effect of rosuvastatin on heart failure (HF) by utilizing a network pharmacology approach and experiments to identify the results. PharmMapper and other databases were mined for information relevant to the prediction of rosuvastatin targets and HF-related targets. Then, the rosuvastatin-HF target gene networks were created in Cytoscape software. Eventually, the targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, we constructed an HF animal model and used rosuvastatin to treat them, identifying the changes in heart function and related protein expression. We further used different cells to explore the mechanisms of rosuvastatin. Thirty-five intersection targets indicated the therapeutic targets linked to HF. GO analysis showed that 481 biological processes, 4 cellular components and 23 molecular functions were identified. KEGG analysis showed 13 significant treatment pathways. In animal experiments, rosuvastatin significantly improved the cardiac function of post-myocardial infarction mice and prevented the development of HF after myocardial infarction by inhibiting IL-1Β expression. Cell experiments showed that rosuvastatin could reduce the expression of IL-1B in HUVEC and THP-1 cells. The therapeutic mechanism of rosuvastatin against HF may be closely related to the inhibition of the expression of apoptosis-related proteins, inflammatory factors, and fibrosis-related genes. However, IL-1Β is one of the most important target genes.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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