{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Phadwal K"],"funding":["The ‘Yangcheng Scholar’ Grant of Guangzhou","National Natural Science Foundation of China","Biotechnology and Biological Sciences Research Council"],"pagination":["21435"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10698150"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2. Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5-1.5 mM) (P < 0.01), with a marked decrease in Runx2 protein expression compared to control cells (P < 0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1 mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P < 0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P < 0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs. Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD."],"journal":["Scientific reports"],"pubmed_title":["Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux."],"pmcid":["PMC10698150"],"funding_grant_id":["(BB/J004316/1; BBS/E/D/20221657)","202032768","82170428"],"pubmed_authors":["Tan X","Koo E","Phadwal K","MacRae VE","Zhu D"],"additional_accession":[]},"is_claimable":false,"name":"Metformin ameliorates valve interstitial cell calcification by promoting autophagic flux.","description":"Calcific aortic valve disease (CAVD) is the most common heart disease of the developed world. It has previously been established that metformin administration reduces arterial calcification via autophagy; however, whether metformin directly regulates CAVD has yet to be elucidated. In the present study we investigated whether metformin alleviates valvular calcification through the autophagy-mediated recycling of Runx2. Calcification was reduced in rat valve interstitial cells (RVICs) by metformin treatment (0.5-1.5 mM) (P < 0.01), with a marked decrease in Runx2 protein expression compared to control cells (P < 0.05). Additionally, upregulated expression of Atg3 and Atg7 (key proteins required for autophagosome formation), was observed following metformin treatment (1 mM). Blocking autophagic flux using Bafilomycin-A1 revealed colocalisation of Runx2 with LC3 puncta in metformin treated RVICs (P < 0.001). Comparable Runx2 accumulation was seen in LC3 positive autolysosomes present within cells that had been treated with both metformin and hydroxychloroquine in combination (P < 0.001). Mechanistic studies employing three-way co-immunoprecipitation with Runx2, p62 and LC3 suggested that Runx2 binds to LC3-II upon metformin treatment in VICs. Together these studies suggest that the utilisation of metformin may represent a novel strategy for the treatment of CAVD.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-05T13:02:30.692Z","creation":"2025-04-05T13:02:30.692Z"},"accession":"S-EPMC10698150","cross_references":{"pubmed":["38052777"],"doi":["10.1038/s41598-023-47774-6"]}}