ArticleRespiratory research2021
CYP2J2 and EETs protect against pulmonary arterial hypertension with lung ischemia-reperfusion injury in vivo and in vitro.
Article in Respiratory research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.Cardiovascular drugs and therapy · 2025Review
- The soluble epoxide hydrolase inhibitor TPPU alleviates Aβ-mediated neuroinflammatory responses in Drosophila melanogaster and cellular models of alzheimer's disease.Journal of inflammation (London, England) · 2025Article
- Apigenin attenuates ischemia-reperfusion-induced pulmonary ferroptosis and fibrosis by activating the Nrf2/HO-1/GPX4 axis in mice.Turkish journal of biology = Turk biyoloji dergisi · 2025Article
- Novel insights into the pathobiology of pulmonary hypertension in heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2024Review
- Sulforaphane alleviates lung ischemia‑reperfusion injury through activating Nrf‑2/HO‑1 signaling.Experimental and therapeutic medicine · 2023Article
- Various effects of 11,12 EET rescue wound healing in a combined model of diabetes and ischemia.Scientific reports · 2023Article
- Classes of Lipid Mediators and Their Effects on Vascular Inflammation in Atherosclerosis.International journal of molecular sciences · 2023Review
- Characterization of 15 CYP2J2 variants identified in the Chinese Han population on the metabolism of ebastine and terfenadineFrontiers in pharmacology · 2023Article
- Soluble Epoxide Hydrolase Inhibitor t-AUCB Ameliorates Vascular Endothelial Dysfunction by Influencing the NF-κB/miR-155-5p/eNOS/NO/IκB Cycle in Hypertensive Rats.Antioxidants (Basel, Switzerland) · 2022Article
- CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators.Molecules (Basel, Switzerland) · 2022Review
- Protective Effect and Mechanism of Traditional Chinese Medicine on Myocardial Ischemia Reperfusion Injury.Evidence-based complementary and alternative medicine : eCAM · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.
methodsCYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by intraperitoneal injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with anoxia/reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.
resultsCYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by the activation of PPARγ; the anti-apoptotic effects might be mediated by the PI3K/AKT pathway.
conclusionsCYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.
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