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

• Main Authors: Arici, M. (Author), Barbuti, A. (Author), Fiorina, P. (Author), Gambini, E. (Author), Genovese, S. (Author), Metallo, A. (Author), Perrucci, G.L (Author), Pompilio, G. (Author), Raucci, A. (Author), Rinaldi, R. (Author), Rocchetti, M. (Author), Rurali, E. (Author), Sacco, E. (Author), Sforza, A. (Author), Vigorelli, V. (Author), Vinci, M.C (Author)
• Format: Article
• Language: English
• Published: BioMed Central Ltd 2022
• Subjects: Cardiovascular disease; CD34+ hematopoietic stem progenitor cells; GLP-1 receptor agonist; Type 2 diabetes mellitus
• Online Access: View Fulltext in Publisher

 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. © 2022, The Author(s).