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Microparticles harbouring Sonic hedgehog morphogen improve the vasculogenesis capacity of endothelial progenitor cells derived from myocardial infarction patients
- Source :
- Cardiovascular Research, Cardiovascular Research, Oxford University Press (OUP), 2019, 115 (2), pp.409-418. ⟨10.1093/cvr/cvy189⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- Aims Endothelial progenitor cells (EPC) play a role in endothelium integrity maintenance and regeneration. Decreased numbers of EPC or their impaired function correlates with an increase in cardiovascular events. Thus, EPC are important predictors of cardiovascular mortality and morbidity. Microparticles carrying Sonic hedgehog (Shh) morphogen (MPShh+) trigger pro-angiogenic responses, both in endothelial cells and in ischaemic rodent models. Here, we propose that MPShh+ regulates EPC function, thus enhancing vasculogenesis, and correcting the defects in dysfunctional EPC obtained from acute myocardial infarction (AMI) patients. Methods and results The mechanisms underlying Shh pathway function and nitric oxide (NO) production in EPC were evaluated. MPShh+ increased both the in vitro and in vivo vasculogenic capacity of EPC isolated from adult human peripheral blood samples. MPShh+ treatment significantly increased the expression of Shh signalling pathway genes (PTCH1, SMO, and GLI1) and masters of pro-angiogenic genes (NOS3, VEGFA, KDR, and KLF2) in EPC. Moreover, MPShh+ increased both the protein expression and activity of eNOS, resulting in increased NO production. Most importantly, MPShh+ improved the vasculogenic capacity of EPC from AMI patients to levels similar to that of EPC from healthy patients. All these effects were due to the activation of Shh pathway. Conclusion MPShh+ increase both the vasculogenesis of EPC and their capacity to produce NO, including EPC from patients who have recently suffered an AMI. This study emphasizes MPShh+ and EPC as potential therapeutic tools for improving vascular regeneration as a treatment for cardiovascular ischaemic disease.
- Subjects :
- 0301 basic medicine
Endothelium
Nitric Oxide Synthase Type III
Physiology
Angiogenesis
[SDV]Life Sciences [q-bio]
Myocardial Infarction
Mice, Nude
Neovascularization, Physiologic
Acute myocardial infarction
030204 cardiovascular system & hematology
Microparticles
Zinc Finger Protein GLI1
03 medical and health sciences
0302 clinical medicine
Vasculogenesis
Cell-Derived Microparticles
Physiology (medical)
Paracrine Communication
medicine
Animals
Humans
Hedgehog Proteins
Progenitor cell
Sonic hedgehog
Angiogenic Proteins
Cells, Cultured
ComputingMilieux_MISCELLANEOUS
Endothelial progenitor cells
biology
business.industry
Nitric oxide
Smoothened Receptor
Hedgehog signaling pathway
Patched-1 Receptor
Vascular endothelial growth factor A
030104 developmental biology
medicine.anatomical_structure
Case-Control Studies
KLF2
embryonic structures
Cancer research
biology.protein
cardiovascular system
Cardiology and Cardiovascular Medicine
business
Signal Transduction
circulatory and respiratory physiology
Subjects
Details
- Language :
- English
- ISSN :
- 00086363
- Database :
- OpenAIRE
- Journal :
- Cardiovascular Research, Cardiovascular Research, Oxford University Press (OUP), 2019, 115 (2), pp.409-418. ⟨10.1093/cvr/cvy189⟩
- Accession number :
- edsair.doi.dedup.....6891c13b7c3d01582ca26583fb841039