VEGF secretion by cardiomyocytes via autocrine signaling modulates myocardial contractile gene expression

摘要

SummaryPost-infarct remodeling is associated with the upregulation of the receptor for advanced glycation end products (RAGE), the induction of its ligand the calcium binding protein S100B and the release of the potent endothelial-cell specific mitogen vascular endothelial growth factor (VEGF). We have recently shown that cardiomyocytes secrete VEGF in response to RAGE ligation by S100B. The newly secreted VEGF in a paracrine manner induces neighbouring myofibroblast proliferation via VEGFR1 ligation [1]. We now show that treatment of neonatal cardiomyocytes with VEGF (10 ng/mL) induces VEGFR-1 tyrosine kinase phosphorylation, Akt phosphorylation and the activation of a-myosin heavy chain (MHC) and the repression of bMHC and skACT, a pattern of gene expression resembling that induced by the thyroid hormone T3.