CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension

Luo, Yongting; Teng, Xiao; Zhang, Lingling; Chen, Jianan; Liu, Zheng; Chen, Xuehui; Zhao, Shuai; Yang, Shaoming; Feng, Jing; Yan, Xiyun

doi:10.1038/s41467-019-11500-6

Cited by 99 publications

(83 citation statements)

References 61 publications

(82 reference statements)

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“…CD146 is a molecule expressed in pulmonary artery smooth muscle cells, and its expression level indicates the severity of the disease. Recently, Luo et al demonstrated that the CD146–HIF1-α axis is responsible for vascular remodeling and PH, suggesting that the inhibition of this axis could be an innovative and effective therapeutic strategy against PH [ 99 ]. Even HIF2-α is able to affect the pathogenesis of PH.…”

Section: Dual Role Of Hypoxia In Acute and Chronic Disease Conditimentioning

confidence: 99%

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Corrado

Fontana

2020

IJMS

122

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The correct concentration of oxygen in all tissues is a hallmark of cellular wellness, and the negative regulation of oxygen homeostasis is able to affect the cells and tissues of the whole organism. The cellular response to hypoxia is characterized by the activation of multiple genes involved in many biological processes. Among them, hypoxia-inducible factor (HIF) represents the master regulator of the hypoxia response. The active heterodimeric complex HIF α/β, binding to hypoxia-responsive elements (HREs), determines the induction of at least 100 target genes to restore tissue homeostasis. A growing body of evidence demonstrates that hypoxia signaling can act by generating contrasting responses in cells and tissues. Here, this dual and controversial role of hypoxia and the HIF signaling pathway is discussed, with particular reference to the effects induced on the complex activities of the immune system and on mechanisms determining cell and tissue responses after an injury in both acute and chronic human diseases related to the heart, lung, liver, and kidney.

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Section: Dual Role Of Hypoxia In Acute and Chronic Disease Conditimentioning

confidence: 99%

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Corrado

Fontana

2020

IJMS

122

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“…HIF-1, composed of the HIF-1α functional subunit and the HIF-1β constitutional subunit ( Luo et al, 2019 ), plays an important role in sensing and adapting to changes in oxygen concentration and is associated with cellular energy metabolism and apoptosis ( Soni and Padwad, 2017 ). HIF-1 is an important target for diseases related to oxygen deprivation ( Albadari et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Re Treatment Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting HIF-1α Ubiquitination

et al. 2020

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bound to VHL substantially decreased following ginsenoside Re treatment. In addition, ginsenoside Re treatment increased the expression of GLUT1 (glucose transporter 1) and REDD1 (regulated in development and DNA damage response 1), which are targets of HIF-1a and are critical for cell metabolism and viability. These results suggested that Ginsenoside Re treatment attenuated the myocardial injury induced by H/R, and the possible mechanism was associated with the inhibition of HIF-1a ubiquitination.

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“…The data that support this study are available from the corresponding author upon reasonable request. Extended Material and Methods section are available in the Supplementary material online [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

Section: Methodsmentioning

confidence: 99%

Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells

Lü

Zhang

et al. 2020

Preprint

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Pulmonary artery hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, which was with limited therapeutic options. It has been proved that cannabidiol (CBD) had antioxidant effects in many cardiovascular diseases, whereas the efficacy of CBD in PAH is unknown. To defined the effect of CBD in PAH, we explored the functions of CBD in both PASMCs proliferation test in vitro, and preventive and therapeutic PAH rodent models in vivo. The roles of CBD in mitochondria function and the oxidant stress were assessed in human PASMCs and PAH mice. We found that CBD significantly inhibited hyperproliferation of hypoxia-induced PASMCs, and intragastrically administered CBD could reverse the pathological changes in both Sugen-hypoxia and MCT- induced PAH mice models. Mechanical analysis demonstrated that CBD alleviated PAH by recovering mitochondrial energy metabolism, normalizing the hypoxia-induced oxidant stress, inhibiting abnormal glycolysis and lactate accumulation in cannabinoids receptors-independent manner. Thus, CBD could be a potential drug for PAH.

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CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension

Cited by 99 publications

References 61 publications

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Hypoxia and HIF Signaling: One Axis with Divergent Effects

Ginsenoside Re Treatment Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting HIF-1α Ubiquitination

Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells

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