Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on VSMC

作者: Marc‐André Raymond , Anik Désormeaux , Patrick Laplante , Normand Vigneault , Janos G. Filep

DOI: 10.1096/FJ.03-0573FJE

关键词: CaspaseParacrine signallingPerlecanVascular endothelial growth factor BMAPK/ERK pathwayBcl-xLCell biologyChemistryVascular endothelial growth factor AApoptosis

摘要: Increased endothelial apoptosis and decreased of vascular smooth muscle cells (VSMC) are central to initiation myo-intimal thickening. We hypothesized that (EC) induces the release anti-apoptotic mediator(s) active on VSMC. found serum-free medium conditioned by apoptotic EC decreases VSMC compared with fresh medium. Inhibition during conditioning a pan-caspase inhibitor ZVAD-FMK blocked factor(s) exposed showed increased ERK 1/2 phosphorylation, enhanced Bcl-xl expression, inhibition p53 expression. Fractionation followed mass spectral analysis identified one bioactive component as C-terminal fragment domain V perlecan. Serum-free supplemented either synthetic peptide containing EGF motif perlecan or chondroitin 4-sulfate, glycosaminoglycan anchored perlecan, phosphorylation protein levels while inhibiting These results suggest proteolytic activity developing downstream activated caspases in initiates degradation pericellular proteoglycans liberation fragments robust impact apoptosis.

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