Skip to Main content Skip to Navigation
Theses

Etude des effets de l'adénosine sur la métalloprotéinase-9 : Implication dans le remodelage ventriculaire

Abstract : Maladaptive remodeling of the left ventricle (LV) is a leading cause of heart failure (HF) after myocardial infarction (MI). It is associated with matrix metalloproteinase (MMP)-9. Although adenosine (Ado) is known to have cardioprotective properties, its role in LV remodeling is still unclear. We hypothesized that Ado could be involved in the regulation of MMP-9. Two waves of inflammatory cells successively infiltrate the heart after MI: first neutrophils then monocytes-macrophages. On the one hand, we have shown that Ado inhibits the secretion of MMP-9 by activated primary human neutrophils. This effect is mediated by the activation of the adenosine-A2a receptor. On the other hand, we cultured human primary macrophages differentiated in vitro from blood monocytes. In sharp contrast to our previous observations with neutrophils, we have shown that Ado enhanced MMP-9 secretion by macrophages. This increase is probably mediated by the adenosine-A3 receptor. We have also shown that Ado improves monocytes migratory capacity and that this effect seems to be consecutive to the stimulation of MMP-9 activity. Finally, preliminary experiments suggest that Ado could have an anti-apoptotic effect on human primary monocytes. These observations thus contributed to the characterization of the effects of Ado on some key processes involved in LV remodeling, including extracellular matrix degradation and inflammatory cells apoptosis. They bring arguments for a paradigm of temporal therapeutic window and could have important implications for therapeutic strategies using Ado and/or its receptors in the treatment of MI and in the prevention of HF.
Document type :
Theses
Complete list of metadata

https://hal.univ-lorraine.fr/tel-01748425
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 11:34:45 AM
Last modification on : Monday, June 29, 2020 - 3:52:06 PM
Long-term archiving on: : Friday, September 14, 2018 - 7:18:11 AM

File

SCD_T_2008_0087_VELOT.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01748425, version 1

Collections

Citation

Émilie Velot. Etude des effets de l'adénosine sur la métalloprotéinase-9 : Implication dans le remodelage ventriculaire. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10087⟩. ⟨tel-01748425⟩

Share

Metrics

Record views

59

Files downloads

184