Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Wilhide, Michael E.; Jones, W. Keith

doi:10.1124/mol.106.024968

Cited by 21 publications

(13 citation statements)

References 46 publications

(73 reference statements)

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“…Our data support the notion that BNP produced by satellite cells proliferating in the ischemic muscle may stimulate the regeneration of neighboring endothelia. Recent studies demonstrated that hypoxia, via stabilization of the hypoxia-inducible factor HIF-1α, induces BNP expression in different cells (8,33). In line with these observations, quantitative RT-PCR analyses demonstrated that BNP mRNA expression in cultured C2C12 cells, a myoblast cell line, was stimulated by hypoxia.…”

Section: Figuresupporting

confidence: 66%

The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice

Kühn¹,

Völker²,

Schwarz³

et al. 2009

J. Clin. Invest.

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Cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) modulate blood pressure and volume by activation of the receptor guanylyl cyclase-A (GC-A) and subsequent intracellular cGMP formation.Here we report what we believe to be a novel function of these peptides as paracrine regulators of vascular regeneration. In mice with systemic deletion of the GC-A gene, vascular regeneration in response to critical hind limb ischemia was severely impaired. Similar attenuation of ischemic angiogenesis was observed in mice with conditional, endothelial cell-restricted GC-A deletion (here termed EC GC-A KO mice). In contrast, smooth muscle cell-restricted GC-A ablation did not affect ischemic neovascularization. Immunohistochemistry and RT-PCR revealed BNP expression in activated satellite cells within the ischemic muscle, suggesting that local BNP elicits protective endothelial effects. Since within the heart, BNP is mainly induced in cardiomyocytes by mechanical load, we investigated whether the natriuretic peptide/GC-A system also regulates angiogenesis accompanying load-induced cardiac hypertrophy. EC GC-A KO hearts showed diminished angiogenesis, mild fibrosis, and diastolic dysfunction. In vitro BNP/GC-A stimulated proliferation and migration of cultured microvascular endothelia by activating cGMP-dependent protein kinase I and phosphorylating vasodilatorstimulated phosphoprotein and p38 MAPK. We therefore conclude that BNP, produced by activated satellite cells within ischemic skeletal muscle or by cardiomyocytes in response to pressure load, regulates the regeneration of neighboring endothelia via GC-A. This paracrine communication might be critically involved in coordinating muscle regeneration/hypertrophy and angiogenesis.

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Section: Figuresupporting

confidence: 66%

The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice

Kühn¹,

Völker²,

Schwarz³

et al. 2009

J. Clin. Invest.

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“…Given the association of natriuretic peptides with proangiogenic activity in several tissues, among other moderately beneficial effects of constitutive, low levels of BNP on the failing myocardium, the induction of BNP by HIF-1a may confer a net beneficial effect, although this remains a hypothetical advantage based on currently available information. 48 Kido et al 49 have reported results similar to those of Heinl-Green et al, discussed above, using a constitutively active construct of HIF-1a driven by a aMHC promoter in transgenic mice. In a murine infarct model, animals expressing the active HIF-1a construct had improved conservation of left ventricular muscle and significantly 50 have also demonstrated that either of two constitutively active HIF-1a constructs -that is with either a Herpes virus VP16 or nuclear factor kappa B (NF-kB) transactivation domain -when expressed in neonatal ventricular myocytes, protected equally well against ischemia reperfusion injury in vitro.…”

Section: Hif-1asupporting

confidence: 58%

Gene therapy progress and prospects: therapeutic angiogenesis for ischemic cardiovascular disease

Vincent¹,

Jiang²,

Boltje³

et al. 2007

Gene Ther

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During the past decade, both in vitro and in vivo studies have provided new insights into the cellular and molecular mechanisms that govern angiogenesis and arteriogenesis. However, therapeutic angiogenesis clinical trials using recombinant protein or gene therapy formulations of single angiogenic growth factors have yielded at best only modest success to date. Among the second generation of angiogenic agents are therapeutic transgenes that enhance expression of two or more proangiogenic cytokines. These include synthetic constructs that mimic that activity of endogenous transcriptional regulators and other upstream, regulatory factors that have the potential to induce formation of morphologically and physiologically functional vessels. These agents are now beginning to be evaluated in clinical trials for patients with advanced ischemic cardiac and peripheral vascular disease.

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“…Under hypoxic conditions, the hydroxylation of Pro402 and Pro564 decreases and HIF-1α protein accumulates. HIF-1α binds to HIF-1β, then translocates to the nuclear compartment and activates the transcription of hypoxia-inducible gene by binding to hypoxia response elements in promoters of a diverse variety of downstream target genes [7][8][9] . Induction of HIF-1α appears to be a crucial step in tissue response to hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor-1α polymorphisms link to coronary artery collateral development and clinical presentation of coronary artery disease

Liu¹,

Liang²,

Zou³

et al. 2013

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims. This study aimed to investigate the association of Hypoxia-inducible factor-1α (HIF-1α) C1772T and G1790A single nucleotide polymorphisms (SNPs) with: incidence, clinical type, severity of coronary atherosclerosis and coronary collaterals of coronary artery disease (CAD). Methods. The clinical data and genomic DNA were gathered in 958 subjects, including 560 controls and 398 patients with CAD. CAD was confirmed with coronary angiography (CAG). The genotypes for two SNPs were determined by high resolution melting after PCR amplification. Results. Neither the HIF-1α C1772T nor the G1790A genotype was significantly associated with CAD and, no gene-gene or gene-environmental interactions were identified. However, both HIF-1α C1772T and G1790A (P<0. Conclusions. We conclude that functional polymorphisms in the HIF-1α gene do not modify CAD risk but they are associated with the formation of coronary collaterals and clinical presentation of CAD.

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Potential Therapeutic Gene for the Treatment of Ischemic Disease: Ad2/Hypoxia-Inducible Factor-1α (HIF-1)/VP16 Enhances B-Type Natriuretic Peptide Gene Expression via a HIF-1-Responsive Element

Cited by 21 publications

References 46 publications

The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice

The natriuretic peptide/guanylyl cyclase–A system functions as a stress-responsive regulator of angiogenesis in mice

Gene therapy progress and prospects: therapeutic angiogenesis for ischemic cardiovascular disease

Hypoxia-inducible factor-1α polymorphisms link to coronary artery collateral development and clinical presentation of coronary artery disease

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