Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension

@article{Zhu2012RoleO1,
  title={Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension},
  author={Daling Zhu and Yajuan Ran},
  journal={The Journal of Physiological Sciences},
  year={2012},
  volume={62},
  pages={163-172}
}
  • Daling Zhu, Yajuan Ran
  • Published 14 February 2012
  • Medicine, Biology
  • The Journal of Physiological Sciences
Pulmonary arterial hypertension (PAH) is a rare disease with a complex aetiology characterized by elevated pulmonary artery resistance, which leads to right heart ventricular afterload and ultimately progressing to right ventricular failure and often death. In addition to other factors, metabolites of arachidonic acid cascade play an important role in the pulmonary vasculature, and disruption of signaling pathways of arachidonic acid plays a central role in the pathogenesis of PAH. 15… 

12-Lipoxygenase and 12-hydroxyeicosatetraenoic acid regulate hypoxic angiogenesis and survival of pulmonary artery endothelial cells via PI3K/Akt pathway.

  • Chen ZhangCui Ma Daling Zhu
  • Biology, Medicine
    American journal of physiology. Lung cellular and molecular physiology
  • 2018
TLDR
It is established that hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic acid through stimulation of 12-lipoxygenase, whereas it inhibits the serum deprivation-induced apoptotic responses underHypoxia, which may have significant implications for understanding of pulmonary hypertension.

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The three-tier-estrogen effects in PAH concept is proposed, which may offer reconciliation of the opposing effects of E2 inPAH and may provide a better understanding of the complex mechanisms by which EMet affects the pulmonary circulation–right ventricular interaction in PAh.

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The Role of Sex in the Pathophysiology of Pulmonary Hypertension.

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Several lines of evidence point towards estrogen being pathogenic in the pulmonary circulation, and thus increasing the risk of females developing PAH, and downstream metabolites such as 16α-hydroxyestrone are upregulated in several forms of experimental pulmonary hypertension (PH).

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References

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15-hydroxyeicosatetraenoic acid depressed endothelial nitric oxide synthase activity in pulmonary artery.

TLDR
The data suggest that eNOS/NO pathway is involved in PA constrictions induced by 15-HETE and that 15- HETE depresses eN OS activity by phosphorylation in Thr495 site, and the protein interaction between phospho-eNOS and 15-LO is discovered for the first time.

The role of ERK1/2 in 15-HETE-inhibited apoptosis in pulmonary arterial smooth muscle cells

TLDR
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ROCK pathway participates in the processes that 15‐hydroxyeicosatetraenoic acid (15‐HETE) mediated the pulmonary vascular remodeling induced by hypoxia in rat

TLDR
Findings indicate that 15‐HETE protects PASMC from apoptosis, contributing to pulmonary vascular medial thickening, and the effect is, at least in part, mediated via the ROCK pathway.

Hypoxia suppresses Kv 2.1 channel expression through endogenous 15-hydroxyeicosatetraenoic acid in rat pulmonary artery

TLDR
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TLDR
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TLDR
Results suggest that 15-HETE may mediate the up-regulation of ROK expression through G-protein and tyrosine kinase pathways under hypoxic condition, leading to PA vasoconstriction.
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