Hypoxia-Inducible Factor-1α and-2α Additively Promote Endothelial Vasculogenic Properties

被引：13

作者：

Ben-Shoshan, Jeremy ^{[1
,2
]}

Maysel-Auslender, Sofia ^{[1
,2
]}

Luboshits, Galia ^{[1
,2
]}

Barshack, Iris ^{[2
,3
]}

Polak-Charcon, Sylvie ^{[3
]}

Tzahor, Eldad ^{[4
]}

Keren, Gad ^{[1
,2
]}

George, Jacob ^{[1
,2
]}

机构：

[1] Tel Aviv Sourasky Med Ctr, Dept Cardiol, IL-64239 Tel Aviv, Israel

[2] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel

[3] Chaim Sheba Med Ctr, Inst Pathol, IL-52621 Tel Hashomer, Israel

[4] Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel

来源：

JOURNAL OF VASCULAR RESEARCH | 2009年 / 46卷 / 04期

关键词：

Hypoxia-inducible factors; Endothelial cells; Cytokine expression; Vasculogenesis; PAS DOMAIN PROTEIN-1; GROWTH-FACTOR; VASCULAR DEVELOPMENT; GENE-EXPRESSION; CELLS DISRUPTS; TRANSCRIPTION; ANGIOGENESIS; ADHESION; HIF-2-ALPHA; MICE;

D O I：

10.1159/000181546

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

Objective: While both play a role in the transcriptional response of hypoxic endothelial cells (ECs), hypoxia- inducible factor-1 alpha (HIF-1 alpha) and HIF-2 alpha differ in their transactivation sites, pointing at potentially different target genes. We studied the discrete and common effects of HIF-1 alpha and HIF-2 alpha on the cytokine expression and vasculogenic properties of ECs. Methods and Results: H5V and bovine aortic ECs were transfected to express HIF-1 alpha, HIF-2 alpha or both. Overexpression of HIF-1 alpha or HIF-2 alpha and, to a greater extent, cotransfection of HIF-1 alpha and HIF-2 alpha resulted in EC activation, as revealed by analysis of the adhesion capacities and adhesion molecule surface expression of ECs. From the paracrine aspect, conditioned medium from HIF-expressing ECs was found to promote the migration and tube formation capacity of wild-type ECs, mostly following HIF-1 alpha and HIF-2 alpha co-expression. Antibody arrays revealed altered expression of multiple cytokines, pointing at consistent additive effects of HIF-1 alpha and HIF-2 alpha on angiogenic protein expression. Finally, HIF-1 alpha and HIF-2 alpha additively promoted vessel formation in vivo, as demonstrated by a Matrigel angiogenesis assay. Conclusion: Our results further clarify the functional roles of HIF-1 alpha and HIF-2 alpha in ECs and for the first time demonstrate a common contribution of HIF-1 alpha and HIF-2 alpha to vasculogenesis. Copyright (C) 2009 S. Karger AG, Basel

引用

页码：299 / 310

页数：12