RGD Reference Report - Knockdown of Nrf2 inhibits the angiogenesis of rat cardiac micro-vascular endothelial cells under hypoxic conditions. - Rat Genome Database

RGD Reference Report - Knockdown of Nrf2 inhibits the angiogenesis of rat cardiac micro-vascular endothelial cells under hypoxic conditions. - Rat Genome Database

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Knockdown of Nrf2 inhibits the angiogenesis of rat cardiac micro-vascular endothelial cells under hypoxic conditions.
Authors:	Kuang, L Feng, J He, G Jing, T
Citation:	Kuang L, etal., Int J Biol Sci. 2013 Jul 7;9(7):656-65. doi: 10.7150/ijbs.5887. Print 2013.
RGD ID:	10412703
Pubmed:	PMID:23904790 (View Abstract at PubMed)
PMCID:	PMC3729008 (View Article at PubMed Central)
DOI:	DOI:10.7150/ijbs.5887 (Journal Full-text)
Angiogenesis plays an important role in myocardial repair after myocardial infarction (MI). Cardiac micro-vascular endothelial cells (CMECs) are important participants in myocardial angiogenesis processes. Recent studies have revealed that Nuclear factor-erythroid 2-related factor 2 (Nrf2), a master transcription factor of endogenous anti-oxidative defense systems, exerts cardio-protection in the cardiovascular system. However, the role of Nrf2 in the process of myocardial angiogenesis and corresponding mechanisms are not fully understood. Thus, the present study investigated the role of Nrf2 in the angiogenesis of rat CMECs to hypoxia. Trans-well assay, three-dimensional Matrigel assay were used to determine cell migration and vascular tube formation. Real-time RT-PCR, ELISA and Western blot were measured mRNA and protein expression. Here, we report that the mRNA and protein expression of Nrf2 and heme oxygenase-1(HO-1) were temporarily upregulated under hypoxic condition. Furthermore, knock down of Nrf2 significantly suppressed the migration and vascular tube formation of rat CMECs to hypoxia, Nrf2 knockdown also significantly decreased HO-1 and vascular endothelial growth factor (VEGF) expression at 48 h after transfection under hypoxic condition. Finally, transfection of CMECs with the Nrf2 over-expressing lentiviral vector upregulated HO-1 expression with a concomitant increase in cell migration and vascular tube formation induced by hypoxia, and this effect was greatly attenuated in the presence of ZnPP (a HO-1 inhibitor). Taken together, these results suggest that Nrf2 may mediate the angiogenesis of CMECs under hypoxic condition, and HO-1 is involved in regulating the angiogenesis of CMECs through Nrf2. Therefore, Nrf2 is a potent regulator of hypoxia-condition mediated angiogenesis in CMECs, which may provide a therapeutic strategy for myocardial repair after MI.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
cellular response to hypoxia		IEP		10412703		RGD
positive regulation of angiogenesis		IMP		10412703		RGD
positive regulation of blood vessel endothelial cell migration		IMP		10412703		RGD

Objects Annotated

Genes (Rattus norvegicus)

Nfe2l2 (NFE2 like bZIP transcription factor 2)

Additional Information