Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure

Autor: Annalisa Sforza, Vera Vigorelli, Erica Rurali, Gianluca Lorenzo Perrucci, Elisa Gambini, Martina Arici, Alessia Metallo, Raffaella Rinaldi, Paolo Fiorina, Andrea Barbuti, Angela Raucci, Elena Sacco, Marcella Rocchetti, Giulio Pompilio, Stefano Genovese, Maria Cristina Vinci
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cardiovascular Diabetology, Vol 21, Iss 1, Pp 1-16 (2022)
Druh dokumentu: article
ISSN: 1475-2840
DOI: 10.1186/s12933-022-01486-9
Popis: Abstract Background Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34+ hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34+ HSPC function. Methods In cord blood (CB)-derived CD34+ HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34+ HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34+ HSPC were evaluated. Results CD34+ HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9–39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects. Conclusion We provided the first evidence that CD34+ HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients.
Databáze: Directory of Open Access Journals
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