A miR-125/Sirtuin-7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35708762", "kind": "science-record", "revision": 4, "content_hash": "sha256:9d9d84196d683841529a29d990f03404b66d1898fb0b7710d704268e89db234e", "created_at": "2026-11-01T18:14:41Z", "updated_at": "2026-11-01T22:06:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A miR-125/Sirtuin-7 pathway drives the pro-calcific potential of myeloid cells in diabetic vascular disease.", "doi": "10.1007/s00125-022-05733-2", "pmid": "35708762", "authors": ["Saula Vigili de Kreutzenberg", "Alessandra Giannella", "Giulio Ceolotto", "Elisabetta Faggin", "Roberta Cappellari", "Marta Mazzucato", "Chiara Fraccaro", "Giuseppe Tarantini", "Angelo Avogaro", "Gian Paolo Fadini"], "journal": "Diabetologia", "year": 2022, "abstract": "AIMS/HYPOTHESIS: Ectopic calcification is a typical feature of diabetic vascular disease and resembles an accelerated ageing phenotype. We previously found an excess of myeloid calcifying cells in diabetic individuals. We herein examined molecular and cellular pathways linking atherosclerotic calcification with calcification by myeloid cells in the diabetic milieu.\nMETHODS: We first examined the associations among coronary calcification, myeloid calcifying cell levels and mononuclear cell gene expression in a cross-sectional study of 87 participants with type 2 diabetes undergoing elective coronary angiography. Then, we undertook in vitro studies on mesenchymal stem cells and the THP-1 myeloid cell line to verify the causal relationships of the observed associations.\nRESULTS: Coronary calcification was associated with 2.8-times-higher myeloid calcifying cell levels (p=0.037) and 50% elevated expression of the osteogenic gene RUNX2 in mononuclear cells, whereas expression of Sirtuin-7 (SIRT7) was inversely correlated with calcification. In standard differentiation assays of mesenchymal stem cells, SIRT7 knockdown activated the osteogenic program and worsened calcification, especially in the presence of high (20 mmol/l) glucose. In the myeloid cell line THP-1, SIRT7 downregulation drove a pro-calcific phenotype, whereas SIRT7 overexpression prevented high-glucose-induced calcification. Through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, high glucose induced miR-125b-5p, which in turn targeted SIRT7 in myeloid cells and was directly associated with coronary calcification.\nCONCLUSIONS/INTERPRETATION: We describe a new pathway elicited by high glucose through the JAK/STAT cascade, involving regulation of SIRT7 by miR-125b-5p and driving calcification by myeloid cells. This pathway is associated with coronary calcification in diabetic individuals and may be a target against diabetic vascular disease.\nDATA AVAILABILITY: RNA sequencing data are deposited in GEO (accession number GSE193510; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE193510 ).", "claims": [{"id": "claim-method", "statement": "Comparison between two group means was performed using unpaired two-tailed Student’s t test. ANOVA with least square difference post hoc test was used to compare three or more groups. Differences between categorical data were assessed by χ2 test. Linear correlation between two continuous variables was explored with Pearson's r and age-adjusted using the partial correlation function.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35708762", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Comparison between two group means was performed using unpaired two-tailed Student’s t test. 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