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

  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},
  • 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
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.

Plasma 12- and 15-Hydroxyeicosanoids are Predictors of Survival in Pulmonary Arterial Hypertension

It was found that 12- and 15-HETE were independent predictors of survival in human PAH, even after adjusting for the REVEAL score, suggesting their potential role as novel biomarkers.

Estradiol Metabolism: Crossroads in Pulmonary Arterial Hypertension

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.

Exosomal 15-LO2 mediates hypoxia-induced pulmonary artery hypertension in vivo and in vitro

Findings indicate a previously unrecognized effect of exosomes and the cargo 15-LO2 in pulmonary vascular homeostasis on the pathogenesis of PH.

NDUFA4L2 in smooth muscle promotes vascular remodeling in hypoxic pulmonary arterial hypertension

It is demonstrated that NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 like 2 (NDUFA4L2) was a proliferation factor and increased in vivo and in vitro through various molecular biology experiments, suggesting NDUFA 4L2 as a potential new therapeutic target for PAH.

The Role of Sex in the Pathophysiology of Pulmonary Hypertension.

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).

ALDH2 (Aldehyde Dehydrogenase 2) Protects Against Hypoxia-Induced Pulmonary Hypertension.

Increased 4-hydroxynonenal level plays a critical role in the development of HPH, suggesting ALDH2 as a potential new therapeutic target for pulmonary hypertension.



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

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

The data indicated that the ERK1/2 kinase is a regulator of PASMC apoptosis, and potential therapeutical strategy for pulmonary hypertension may be developed by targeting at intracellular signaling systems centered by the kinase.

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

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

It is found that Kv2.1 channel expression at the mRNA and protein levels was greatly up-regulated in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary artery (PA) after blockade of endogenous 15-HETE under hypoxic condition.

The two faces of the 15-lipoxygenase in atherosclerosis.

15-HETE suppresses K+ channel activity and inhibits apoptosis in pulmonary artery smooth muscle cells

It is found that 15-HETE enhanced cell survival, suppressed the expression and activity of caspase-3, upregulated bcl-2 and attenuated mitochondrial depolarization, prevented chromatin condensation and partly reversed K+ channel opener-induced apoptosis in PASMCs under serum-deprived conditions.

Role of the G-protein and tyrosine kinase--Rho/ROK pathways in 15-hydroxyeicosatetraenoic acid induced pulmonary vasoconstriction in hypoxic rats.

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.