Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages

Francesco Prattichizzo, Valeria De Nigris, Elettra Mancuso, Rosangela Spiga, Angelica Giuliani, Giulia Matacchione, Raffaella Lazzarini, Fiorella Marcheselli, Rina Recchioni, Roberto Testa, Lucia La Sala, Maria Rita Rippo, Antonio Domenico Procopio, Fabiola Olivieri, Antonio Ceriello

Research output: Contribution to journalArticlepeer-review

Abstract

Diabetic status is characterized by chronic low-grade inflammation and an increased burden of senescent cells. Recently, the senescence-associated secretory phenotype (SASP) has been suggested as a possible source of inflammatory factors in obesity-induced type 2 diabetes. However, while senescence is a known consequence of hyperglycaemia, evidences of SASP as a result of the glycaemic insult are missing. In addition, few data are available regarding which cell types are the main SASP-spreading cells in vivo. Adopting a four-pronged approach we demonstrated that: i) an archetypal SASP response that was at least partly attributable to endothelial cells and macrophages is induced in mouse kidney after in vivo exposure to sustained hyperglycaemia; ii) reproducing a similar condition in vitro in endothelial cells and macrophages, hyperglycaemic stimulus largely phenocopies the SASP acquired during replicative senescence; iii) in endothelial cells, hyperglycaemia-induced senescence and SASP could be prevented by SOD-1 overexpression; and iiii) ex vivo circulating angiogenic cells derived from peripheral blood mononuclear cells from diabetic patients displayed features consistent with the SASP. Overall, the present findings document a direct link between hyperglycaemia and the SASP in endothelial cells and macrophages, making the SASP a highly likely contributor to the fuelling of low-grade inflammation in diabetes.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalRedox Biology
DOIs
Publication statusE-pub ahead of print - Dec 6 2017

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