Paracrine repercussions of preconditioning on angiogenesis and apoptosis of endothelial cells.
The mechanisms of cytoprotection conferred by stress preconditioning remain largely uncharacterized in endothelial cells (EC). We report that stress preconditioning of EC with serum starvation induces the release of soluble mediator(s) that confer resistance to apoptosis, increase proliferation, and enhance angiogenesis in a second set of "non-preconditioned" EC. Preconditioning was found to target specifically the mitochondrial control of apoptosis in EC with increased protein levels of Bcl-2, decreased protein levels of Bax, and decreased cytosolic release of cytochrome c. Regulators of apoptosis acting upstream and downstream of the mitochondria such as p53, cIAP-1, cIAP-2, and XIAP were not altered. Mediators classically associated with preconditioning in other cell types such as adenosine, opioids, and nitric oxide are not implicated in this cytoprotective loop. Blockade of protein kinase C-dependent signaling inhibited cytoprotection of EC. Further characterization of this paracrine pathway should provide insights into the molecular regulation of preconditioning in endothelial cells.
Raymond
Marc-André
MA
CRCHUM, Notre-Dame Hospital, University of Montreal, Montréal, Québec H2L 4M1, Canada.
Vigneault
Normand
N
Luyckx
Valerie
V
Hébert
Marie-Josée
MJ
D017209:Apoptosis; D001685:Biological Factors / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D019610:Cytoprotection; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001685:Biological Factors; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D011493:Protein Kinase C