Centro Cardiologico Monzino IRCCS
Published April 9, 2022 | Version v1
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Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure

Authors/Creators

  • 1. ROR icon Centro Cardiologico Monzino
  • 2. ROR icon University of Milan
  • 3. ROR icon University of Milano-Bicocca
  • 4. Università degli Studi di Milano-Bicocca

Description

This record contains raw data related to the article "Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure"

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.

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Additional details

Related works

Is supplement to
Data paper: 10.1186/s12933-022-01486-9 (DOI)

Funding

Ministero della Salute
Ricerca Corrente • RC 2019 2764158