Dataset Information

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

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.

SUBMITTER: Sforza A

PROVIDER: S-EPMC8994898 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Liraglutide preserves CD34<sup>+</sup> stem cells from dysfunction Induced by high glucose exposure.

Sforza Annalisa A Vigorelli Vera V Rurali Erica E Perrucci Gianluca Lorenzo GL Gambini Elisa E Arici Martina M Metallo Alessia A Rinaldi Raffaella R Fiorina Paolo P Barbuti Andrea A Raucci Angela A Sacco Elena E Rocchetti Marcella M Pompilio Giulio G Genovese Stefano S Vinci Maria Cristina MC

Cardiovascular diabetology 20220409 1

<h4>Background</h4>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<sup>+</sup> 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 i ...[more]

PMID: 35397526

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Project description:Ex vivo monitored human CD34+ stem cells (SCs) injected into myocardium scar tissue have shown real benefits for the recovery of patients with myocardial infarctions. They have been used previously in clinical trials with hopeful results and are expected to be promising for cardiac regenerative medicine following severe acute myocardial infarctions. However, some debates on their potential efficacy in cardiac regenerative therapies remain to be clarified. To elucidate the levels of CD34+ SC implication and contribution in cardiac regeneration, better identification of the main regulators, pathways, and genes involved in their potential cardiovascular differentiation and paracrine secretion needs to be determined. We first developed a protocol thought to commit human CD34+ SCs purified from cord blood toward an early cardiovascular lineage. Then, by using a microarray-based approach, we followed their gene expression during differentiation. We compared the transcriptome of undifferentiated CD34+ cells to those induced at two stages of differentiation (i.e., day three and day fourteen), with human cardiomyocyte progenitor cells (CMPCs), as well as cardiomyocytes as controls. Interestingly, in the treated cells, we observed an increase in the expressions of the main regulators usually present in cardiovascular cells. We identified cell surface markers of the cardiac mesoderm, such as kinase insert domain receptor (KDR) and the cardiogenic surface receptor Frizzled 4 (FZD4), induced in the differentiated cells in comparison to undifferentiated CD34+ cells. The Wnt and TGF-β pathways appeared to be involved in this activation. This study underlined the real capacity of effectively stimulated CD34+ SCs to express cardiac markers and, once induced, allowed the identification of markers that are known to be involved in vascular and early cardiogenesis, demonstrating their potential priming towards cardiovascular cells. These findings could complement their paracrine positive effects known in cell therapy for heart disease and may help improve the efficacy and safety of using ex vivo expanded CD34+ SCs.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

Liraglutide preserves CD34<sup>+</sup> stem cells from dysfunction Induced by high glucose exposure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

Liraglutide preserves CD34<sup>+</sup> stem cells from dysfunction Induced by high glucose exposure.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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