PMID- 35571082 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 13 DP - 2022 TI - The Natural Product Andrographolide Ameliorates Calcific Aortic Valve Disease by Regulating the Proliferation of Valve Interstitial Cells via the MAPK-ERK Pathway. PG - 871748 LID - 10.3389/fphar.2022.871748 [doi] LID - 871748 AB - Calcific aortic valve disease (CAVD) is an active pathobiological process that involves fibrosis and calcification of aortic valve leaflets, thereby causing cardiac hemodynamic changes and eventually heart failure. Cell proliferation changes at the initial stage of CAVD are an important target for pharmaceutical intervention. This study aimed to investigate whether andrographolide (AGP) could inhibit the proliferation of valve interstitial cells (VICs) in vitro and in vivo to delay the process of CAVD. Cell proliferative factors were tested in both healthy and CAVD aortic valve samples. Cell cycle, cell growth, and calcification of VICs were assessed using flow cytometry, CCK8 assay, EdU staining, and Alizarin Red S staining. The expression of cell proliferative factors and osteogenic factors were quantified by qRT-PCR or immunofluorescence staining. The interaction between AGP and ERK (extracellular regulated protein kinases) was detected by molecular docking. In addition, a high-fat diet-fed animal model was used to verify the effect of AGP on CAVD in vivo. In conclusion, we found that AGP ameliorates aortic valve incrassation by inhibiting cell proliferation via the MAPK-ERK signaling pathway. Therefore, AGP is a promising drug that prevents the occurrence of CAVD via regulating cell proliferation. CI - Copyright (c) 2022 Huang, Liu, Liu, Dong and Chen. FAU - Huang, Yuming AU - Huang Y AD - Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Liu, Ming AU - Liu M AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Liu, Chungeng AU - Liu C AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Dong, Nianguo AU - Dong N AD - Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Chen, Liang AU - Chen L AD - Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article DEP - 20220429 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC9100698 OTO - NOTNLM OT - CAVD OT - MAPK /ERK2 pathway OT - andrographolide OT - cell proliferation OT - valve interstitial cell COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/05/17 06:00 MHDA- 2022/05/17 06:01 PMCR- 2022/04/29 CRDT- 2022/05/16 03:54 PHST- 2022/02/08 00:00 [received] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/05/16 03:54 [entrez] PHST- 2022/05/17 06:00 [pubmed] PHST- 2022/05/17 06:01 [medline] PHST- 2022/04/29 00:00 [pmc-release] AID - 871748 [pii] AID - 10.3389/fphar.2022.871748 [doi] PST - epublish SO - Front Pharmacol. 2022 Apr 29;13:871748. doi: 10.3389/fphar.2022.871748. eCollection 2022.