l-carnosine and verapamil inhibit hypoxia-induced expression of hypoxia inducible factor (HIF-1 α) in H9c2 cardiomyoblasts

2002 ◽  
Vol 45 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Lalita A. Bharadwaj ◽  
Gerald F. Davies ◽  
Ilungo J. Xavier ◽  
Nick Ovsenek
Keyword(s):  
Hypoxia Inducible Factor ◽  
Induced Expression ◽  
H9c2 Cardiomyoblasts

Hypoxia and hypoxia-inducible factor-1α promote growth factor-induced proliferation of human vascular smooth muscle cells

2006 ◽  
Vol 290 (6) ◽  
pp. H2528-H2534 ◽  
Author(s):  
Kelly Schultz ◽  
Barry L. Fanburg ◽  
Debbie Beasley
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Hypoxia Inducible Factor ◽  
Muscle Cells ◽  
Cyclin A ◽  
Induced Expression ◽  
Moderate Hypoxia

Hypoxia is thought to be a stimulus for the excessive proliferation of vascular smooth muscle cells (VSMC) that contributes to pulmonary hypertension, but the mechanisms involved are unknown. Here we tested whether hypoxia-inducible factor 1-α (HIF-1α), a master regulator of the transcriptional response to hypoxia, is involved in the enhanced mitogen-induced proliferative responses of hypoxic VSMC. Exposure to moderate hypoxia (5% O2) enhanced the proliferative responses of human pulmonary artery SMC (HPASMC) to mitogens including platelet-derived growth factor (PDGF), fibroblast growth factor 2 (FGF-2), and epidermal growth factor (EGF), compared with those in normoxia (20% O2). Moderate hypoxia elicited increased cellular HIF-1α levels, shown by Western blot analysis, and also enhanced PDGF-, FGF-2-, and EGF-induced expression of HIF-1α. Knockdown of HIF-1α or HIF-1β levels in HPASMC with specific small interfering RNAs inhibited FGF-2-stimulated proliferation of HPASMC incubated in either 5% or 20% O2 but failed to inhibit the comitogenic effect of hypoxia. Knockdown of HIF-1α similarly inhibited PDGF-stimulated proliferation, whereas HIF-2α knockdown had no effect on HPASMC proliferation. Knockdown of HIF-1α expression also inhibited growth factor-induced expression of cyclin A. We conclude that HIF-1α promotes proliferative responses of human VSMC to FGF-2, PDGF, and EGF by mechanisms that may involve HIF-1-dependent expression of cyclin A, but HIF is apparently not crucial to the enhancement of FGF-2-, PDGF-, and EGF-induced proliferation of VSMC that occurs during hypoxia.

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