Acute hypoxia promotes the liver angiogenesis of largemouth bass (Micropterus salmoides) by HIF - Dependent pathway

Abstract

A 24-h hypoxia exposure experiment was conducted to determine how hypoxia exposure induce liver angiogenesis in largemouth bass. Nitrogen (N2) was pumped into water to exclude dissolved oxygen into 1.2 ± 0.2 mg/L, and liver tissues were sampled during hypoxia exposure of 0 h, 4 h, 8 h, 12 h, 24 h and re-oxygenation for 12 h. Firstly, the results showed that hypoxia exposure promoted the angiogenesis occurrence by immunohistochemical analysis of vascular endothelial growth factor receptor 2 (VEGFR2). Secondly, the concentration of vasodilation factor increased and it's activity was elevated during 8 h exposure, such as nitric oxide (NO) and nitric oxide synthase (NOS) (p < 0.05). Thirdly, hypoxia exposure promoted angiogenesis through up-regulation the expression of matrix metalloproteinase 2 (MMP-2), jagged, protein kinase B (AKT), phosphoinositide-3-kinase (PI3K), mitogen-activated protein kinase (MAPK) at 4 h; contrarily, the expression of inhibiting angiogenesis genes presented up-regulated at 8 h (p < 0.05), such as matrix metalloproteinase inhibitor-2 (TIMP-2), matrix metalloproteinase inhibitor-3 (TIMP-3). Finally, the genes and proteins that regulate angiogenesis presented obvious chronological order. Parts of them promoted the budding and extension of blood vessels were up-regulated during 4 h–8 h (p < 0.05), such as vascular endothelial growth factor a (VEGFA), VEGFR2, monocarboxylic acid transporter 1 (MCT1), CD147, prolyl hydroxylase (PHD), nuclear factor kappa-B (NF-κB); other part of them promoted blood vessel maturation were highly expressed during 12 h–24 h (p < 0.05), such as angiogenin-1 (Ang-1) and angiogenin-2 (Ang-2). In short, acute hypoxia can promote the liver angiogenesis of largemouth bass by HIF - dependent pathway.