Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease

Wang, Wei; Xu, Baohui; Xuan, Haojun; Ge, Yali; Wang, Yan; Wang, Lixin; Huang, Jianhua; Fu, Weiguo; Michie, Sara A.; Dalman, Ronald L.

doi:10.1016/j.jvs.2017.09.030

Cited by 59 publications

(66 citation statements)

References 47 publications

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“…Further, more than one hundred genes have been identified to be governed by mammalian HIF during O 2 deprivation [42,43]. The involvement of HIF-1α in diseases of the vascular wall, including atherosclerosis, carotid stenosis, and aneurysms, has recently been proposed [44][45][46][47][48][49]. Indeed, insufficient expression of HIF is associated with CVD [50,51].…”

Section: Hypoxia-inducible Factorsmentioning

confidence: 99%

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Alique

Sánchez-López

Bodega

et al. 2020

Cells

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Aging is one of the hottest topics in biomedical research. Advances in research and medicine have helped to preserve human health, leading to an extension of life expectancy. However, the extension of life is an irreversible process that is accompanied by the development of aging-related conditions such as weakness, slower metabolism, and stiffness of vessels. It also debated that aging can be considered an actual disease with aging-derived comorbidities, including cancer or cardiovascular disease. Currently, cardiovascular disorders, including atherosclerosis, are considered as premature aging and represent the first causes of death in developed countries, accounting for 31% of annual deaths globally. Emerging evidence has identified hypoxia-inducible factor-1α as a critical transcription factor with an essential role in aging-related pathology, in particular, regulating cellular senescence associated with cardiovascular aging. In this review, we will focus on the regulation of senescence mediated by hypoxia-inducible factor-1α in age-related pathologies, with particular emphasis on the crosstalk between endothelial and vascular cells in age-associated atherosclerotic lesions. More specifically, we will focus on the characteristics and mechanisms by which cells within the vascular wall, including endothelial and vascular cells, achieve a senescent phenotype.

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Section: Hypoxia-inducible Factorsmentioning

confidence: 99%

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Alique

Sánchez-López

Bodega

et al. 2020

Cells

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“…Digoxin is known as a selective inhibitor of HIF-1α translation, and has a suppressive effect of initiation and progression of AAAs in in vivo models [17, 26]. Recent studies have shown that digoxin inhibits the differentiation of T helper 17 (Th17) cells, and production of interleukin (IL)-17A [27, 28].…”

Section: Discussionmentioning

confidence: 99%

Digoxin Attenuates Receptor Activation of NF-κB Ligand-Induced Osteoclastogenesis in Macrophages

Igari

Kelly

Yamanouchi³

2019

J Vasc Res

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Background: Even though hypoxia-inducible factor-1α (HIF-1α) is among the transcriptional factors demonstrated to contribute to the formation of abdominal aortic aneurysms (AAAs), the precise mechanism has been unclear. Digoxin is known as an inhibitor of HIF-1α, and shows a protective effect against the progression of AAAs. Objectives: We tested the effect of digoxin on osteoclastogenesis (OCG) and examined the pathway through which digoxin exerts inhibition of HIF-1α. Materials and Methods: RAW 264.7 macrophage cells were cultured and stimulated by soluble receptor activator of NF-κB ligand (sRANKL) with or without digoxin. First, we tested the effect of digoxin to attenuate macrophage activation, which led to OCG, characterized by tartrate-resistant acid phosphatase (TRAP)-positive macrophages (TPMs). Results: The activation of TPMs stimulated by sRANKL was attenuated by digoxin treatment. Furthermore, the receptor activator of NF-κB (RANK)/receptor activator of NF-κB ligand (RANKL) complex signaling pathway, which is stimulated by HIF-1α, was downregulated by digoxin treatment. Conclusions: These results show that digoxin attenuates OCG. By inhibition of HIF-1α, digoxin decreases OCG through the downregulation of the RANK/RANKL signaling pathway. Therefore, digoxin is a potential candidate for medical treatment of AAAs.

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“…31) A similar observation was seen using pharmacological inhibition of HIF-1 in an elastase-induced mouse AAA model. 72) In contrast, it has been reported that expression of HIF-1 in myeloid lineage protects AAA formation. In myeloidspecific HIF-1α and ApoE double-knockout mice, deletion of HIF-1 increased aneurysm diameter after infusion of Ang II.…”

Section: Target Of Transcription Factors To Treat Aaamentioning

confidence: 97%

“…Activation of HIF-1 was also observed in human AAA tissues. 72) In addition, silencing of HIF-1 using shRNA reduced AAA diameter in an Ang II-induced ApoE-deficient mouse AAA model via inhibition of upregulation of MMPs and inflammatory and angiogenic factors. 31) A similar observation was seen using pharmacological inhibition of HIF-1 in an elastase-induced mouse AAA model.…”

Section: Target Of Transcription Factors To Treat Aaamentioning

confidence: 99%

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

Miyake

Kurashiki

et al. 2019

Annals of Vascular Diseases

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Abdominal aortic aneurysm (AAA) is considered to be a potent life-threatening disorder in elderly individuals. Although many patients with a small AAA are detected during routine abdominal screening, there is no effective therapeutic option to prevent the progression or regression of AAA in the clinical setting. Recent advances in molecular biology have led to the identification of several important molecules, including microRNA and transcription factor, in the process of AAA formation. Regulation of these factors using nucleic acid drugs is expected to be a novel therapeutic option for AAA. Nucleic acid drugs can bind to target factors, mRNA, microRNA, and transcription factors in a sequence-specific fashion, resulting in a loss of function of the target molecule at the transcriptional or posttranscriptional level. Of note, inhibition of a transcription factor using a decoy strategy effectively suppresses experimental AAA formation, by regulating the expression of several genes associated with the disease progression. This review focuses on recent advances in molecular therapy of using nucleic acid drugs to treat AAA.

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Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease

Cited by 59 publications

References 47 publications

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Hypoxia-Inducible Factor-1α: The Master Regulator of Endothelial Cell Senescence in Vascular Aging

Digoxin Attenuates Receptor Activation of NF-κB Ligand-Induced Osteoclastogenesis in Macrophages

Molecular Pharmacological Approaches for Treating Abdominal Aortic Aneurysm

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