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

Cardiovasc Diabetol. 2022 Apr 9;21(1):51. doi: 10.1186/s12933-022-01486-9.

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.

Keywords: CD34+ hematopoietic stem progenitor cells; Cardiovascular disease; GLP-1 receptor agonist; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CXCL12
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucose / toxicity
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Liraglutide* / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Stem Cells / metabolism

Substances

  • Chemokine CXCL12
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Proto-Oncogene Proteins c-akt
  • Glucose