Expression of 15-lipoxygenases in pulmonary arteries after hypoxia

Liu, Ye; Tang, Xiaobo; Lu, Changlian; Wang, Han; Guo, Shouli; Zhu, Daling

doi:10.1080/00313020903040970

Cited by 7 publications

(8 citation statements)

References 10 publications

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“…The expressions of BMP4 mRNA increased significantly in 60 min and protein increased significantly in 120 min exposure to hypoxia. Combined with our previously study which showed the 15‐LO1/2 expression started rising after 2–4 h of hypoxia and peaked at 8–12 h (Liu et al, ), these results suggest that BMP4 may an important upstream mediator in hypoxia‐stimulated 15‐LO up‐regulation, and that 15‐LO1/2 may interact with BMP4 in PASMCs.…”

Section: Resultssupporting

confidence: 82%

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15-Lipoxygenase Promotes Chronic Hypoxia-Induced Phenotype Changes of PASMCs Via Positive Feedback-Loop of BMP4

Wei

Lü

et al. 2015

J. Cell. Physiol.

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Our laboratory has previously demonstrated that 15-lipoxygenase (15-LO)/15-hydroxyeicosatetr-aenoic acid (15-HETE) is involved in hypoxic pulmonary arterial hypertension (PAH). Phenotypical alterations of vascular smooth muscle cells are considered to be an important stage in the development of PAH, whereas the underlying mechanisms and signaling systems are still unclear. Here, we determined the contribution of 15-LO/15-HETE signaling in the hypoxia-induced phenotype changes of pulmonary arterial smooth muscle cells (PASMCs). To accomplish this, cellular and molecular changes in pulmonary vascular remodeling were detected in PAH patients and rats exposed to hypoxia. We found that the hypoxia-induced alterations in PASMCs phenotypes were reversed by the inhibition of 15-LO/15-HETE or inhibition of BMP4/BMPRI. Hypoxia-induced 15-LO1/2 expression in rat PASMCs was significantly abolished by small interfering RNA targeted at BMP4. Meanwhile, BMP4/BMPRI-15-LO/15-HETE had a positive feedback mechanism. Furthermore, ERK and p38MAPK act as the downstream of the 15-LO/15-HETE-BMP4/BMPRI signaling. Our results suggest that chronic hypoxia promotes phenotypical alterations of PASMCs due to the interaction between 15-LO/15-HETE and BMP4/BMPRI. Our study reveals a novel mechanism of hypoxia-induced pulmonary vascular remodeling and suggested new therapeutic strategies for the targeting of 15-LO/15-HETE and BMP4/BMPRI in PAH treatment.

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Section: Resultssupporting

confidence: 82%

“…15-LO-1 and 15-LO-2 are two types of 15-LO isoenzymes, and the homology between them is 31.6%. It has been identified previously that they distribute differently in pulmonary arterial cells (Liu et al, 2009). Here, we found that BMP4 is necessary for the hypoxia-induced 15-LO1/2 expression.…”

Section: Discussionmentioning

confidence: 98%

15-Lipoxygenase Promotes Chronic Hypoxia-Induced Phenotype Changes of PASMCs Via Positive Feedback-Loop of BMP4

Wei

Lü

et al. 2015

J. Cell. Physiol.

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“…Here, we found that NF-κB, a well-known transcriptional factor regulating the transcription of a number of genes including 5-and 12-lipoxygenase, 14,21 is necessary for the hypoxia-induced 15-LO1/2 expression. 15-LO1/2 transcripts increase 2 hours after hypoxia exposure in PAECs, a time properly following the activation of NF-κB.…”

Section: Discussionmentioning

confidence: 93%

“…The 15-LO1/2 expression started rising after 2 to 4 hours of hypoxia and peaked at 8 to 12 hours. 14,21 We first used the transcriptional inhibitor actinomycin D to explore the regulatory mechanism of 15-LO1/2 by hypoxia. The augmentation of 15-LO isoenzymes with hypoxia was nearly totally eliminated by actinomycin D (Figure 6B and 6C), indicating that hypoxia upregulate 15-LO isoenzymes by increasing gene transcription.…”

Section: Hypoxia Induces the Upregulation Of 15-lo Transcript Via Nf-κbmentioning

confidence: 99%

15-Lipoxygenase Promotes Chronic Hypoxia–Induced Pulmonary Artery Inflammation via Positive Interaction With Nuclear Factor-κB

Rao²,

Liu³

et al. 2013

ATVB

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Objective-Our laboratory has previously demonstrated that 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) is involved in hypoxic pulmonary arterial hypertension. Chronic hypoxia-induced vascular inflammation has been considered as an important stage in the development of pulmonary arterial hypertension. Here, we determined the contribution of 15-HETE in the hypoxia-induced pulmonary vascular inflammation. Approach and Results-Chronic hypoxia-induced monocyte/macrophage infiltration and the expressions of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed in hypoxic rat model and cultured pulmonary arterial endothelium cells using immunochemistry methods. We found that monocyte/macrophage infiltration and the expressions of intercellular adhesion molecules under hypoxia were markedly inhibited by 15-HETE inhibitors or 15-LO1/2 small interfering RNA. In addition, exogenous 15-HETE enhanced the expression of both adhesion molecules in pulmonary arterial endothelium cells in a time-dependent manner. Hypoxia-induced 15-LO1/2 expression in rat pulmonary arterial endothelium cells was significantly abolished by nuclear factor-κB inhibitors. Meanwhile, nuclear factor-κB activity was enhanced prominently by the 15-LO1/2 product, 15-HETE, suggesting a positive feedback mechanism. Conclusions-Taken together, our results suggest that chronic hypoxia promotes monocyte infiltration into the vasculature and adhesion molecules upregulation in pulmonary arterial endothelium cells via a positive interaction between 15-LO/15-HETE and nuclear factor-κB. Our study revealed a novel mechanism underlying hypoxia-induced pulmonary arterial inflammation and suggested new therapeutic strategies targeting 15-LO/15-HETE and nuclear factor-κB in the treatment of pulmonary arterial hypertension. (Arterioscler Thromb Vasc Biol. 2013;33:971-979.)

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“…15-LOX-1 activity is detected in resting monocytes, macrophages and dendritic cells and is up-regulated by the Th2 cytokines IL4 and IL13 (Nassar et al 1994, Spanbroek et al 2001 and by hypoxia (Liu et al 2009). 15-LOX-2 expression is predominantly observed in epithelial tissues, but it is also up-regulated by macrophages in response to hypoxia (Rydberg et al 2004).…”

Section: Box 1 Transcellular Synthesis Of Eicosanoidsmentioning

confidence: 99%

Molecular regulators of resolution of inflammation: potential therapeutic targets in the reproductive system

Hutchinson

Rajagopal²,

Sales³

et al. 2011

Reproduction

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Inflammatory processes are central to reproductive events including ovulation, menstruation, implantation and labour, while inflammatory dysregulation is a feature of numerous reproductive pathologies. In recent years, there has been much research into the endogenous mechanisms by which inflammatory reactions are terminated and tissue homoeostasis is restored, a process termed resolution. The identification and characterisation of naturally occurring pro-resolution mediators including lipoxins and annexin A1 has prompted a shift in the field of anti-inflammation whereby resolution is now observed as an active process, triggered as part of a normal inflammatory response. This review will address the process of resolution, discuss available evidence for expression of pro-resolution factors in the reproductive tract and explore possible roles for resolution in physiological reproductive processes and associated pathologies. Reproduction (2011) 142 15-28

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Expression of 15-lipoxygenases in pulmonary arteries after hypoxia

Cited by 7 publications

References 10 publications

15-Lipoxygenase Promotes Chronic Hypoxia-Induced Phenotype Changes of PASMCs Via Positive Feedback-Loop of BMP4

15-Lipoxygenase Promotes Chronic Hypoxia-Induced Phenotype Changes of PASMCs Via Positive Feedback-Loop of BMP4

15-Lipoxygenase Promotes Chronic Hypoxia–Induced Pulmonary Artery Inflammation via Positive Interaction With Nuclear Factor-κB

Molecular regulators of resolution of inflammation: potential therapeutic targets in the reproductive system

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