Vasohibin1, a new IRES trans-acting factor for sequential induction of angiogenic factors in hypoxia

Hypoxia, a major inducer of angiogenesis, is known to trigger major changes of gene expression at the transcriptional level. Furthermore, global protein synthesis is blocked while internal ribosome entry sites (IRES) allow specific mRNAs to be translated. Here we report the transcriptome and translatome signatures of (lymph)angiogenic genes in hypoxic HL-1 cardiomyocytes: most genes are not induced at the transcriptome-, but at the translatome level, including all IRES-containing mRNAs. Our data reveal sequential activation of (lymph)angiogenic mRNA IRESs in early hypoxia. We identify vasohibin1 (VASH1) as an IRES trans-acting factor (ITAF) able to activate the earliest induced FGF1 IRES while it inhibits the other IRESs. Thus this new ITAF may have opposite effects on IRES activities in the steps of early hypoxia. These data suggest that IRESome composition varies at different stages of hypoxia, leading to sequential induction of (lymph)angiogenic factors required to form new functional vessels in ischemic heart.