ArticleArteriosclerosis, thrombosis, and vascular biology2012
Lysophosphatidic acid signaling protects pulmonary vasculature from hypoxia-induced remodeling.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.Respiratory research · 2014Trial
- ENPP2 Protects Mouse Myocardium from Ischemia-Reperfusion-Induced Ferroptosis Injury Via the SIRT1/PGC-1α/NRF1 Pathway.Applied biochemistry and biotechnology · 2026Article
- Pharmacological Blockade of LPAR1 Does Not Provide Neuroprotection in a Rat Model of Ocular Hypertensive Glaucoma.Translational vision science & technology · 2026Article
- Glycerophospholipid and Sphingosine- 1-phosphate Metabolism in Cardiovascular Disease: Mechanisms and Therapeutic Potential.Journal of cardiovascular translational research · 2025Review
- Lysophosphatidic acid improves development of porcine somatic cell nuclear transfer embryos.Journal of animal science and technology · 2024Article
- Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation.Development (Cambridge, England) · 2023Article
- Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2023Review
- Bioactive lipids and metabolic syndrome-a symposium report.Annals of the New York Academy of Sciences · 2022Article
- Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?Metabolites · 2021Article
- ENPP4 overexpression is associated with no recovery from Barrett's esophagus.International journal of clinical and experimental pathology · 2020Article
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Regulation of PLPP3 gene expression by NF-κB family transcription factors.The Journal of biological chemistry · 2019Article
- RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line.Oncotarget · 2018Article
- Lysophosphatidic acid counteracts glucagon-induced hepatocyte glucose production via STAT3.Scientific reports · 2017Article
- Role of oxidized lipids in pulmonary arterial hypertension.Pulmonary circulation · 2016Review
- Recent advances in targeting the autotaxin-lysophosphatidate-lipid phosphate phosphatase axis in vivo.Journal of biomedical research · 2016Review
- Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction.Experimental and therapeutic medicine · 2016Article
- Deficiency or inhibition of lysophosphatidic acid receptor 1 protects against hyperoxia-induced lung injury in neonatal rats.Acta physiologica (Oxford, England) · 2016Article
- Homology modeling and docking studies of ENPP4: a BCG activated tumoricidal macrophage protein.Lipids in health and disease · 2016Article
- Lysophospholipid mediators in the vasculature.Experimental cell research · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveLysophosphatidic acid (LPA) is a bioactive lipid molecule produced by the plasma lysophospholipase D enzyme autotaxin that is present at ≥100 nmol/L in plasma. Local administration of LPA promotes systemic arterial remodeling in rodents. To determine whether LPA contributes to remodeling of the pulmonary vasculature, we examined responses in mice with alterations in LPA signaling and metabolism. METHODS AND
resultsEnpp2(+/-) mice, which are heterozygous for the autotaxin-encoding gene and which have reduced expression of autotaxin/lysophospholipase D and approximately half normal plasma LPA, were hyperresponsive to hypoxia-induced vasoconstriction and remodeling, as evidenced by the development of higher right ventricular (RV) systolic pressure, greater decline in peak flow velocity across the pulmonary valve, and a higher percentage of muscularized arterioles. Mice lacking LPA(1) and LPA(2), 2 LPA receptors abundantly expressed in the vasculature, also had enhanced hypoxia-induced pulmonary remodeling. With age, Lpar1(-/-)2(-/-) mice spontaneously developed elevated RV systolic pressure and RV hypertrophy that was not observed in Lpar1(-/-) mice or Lpar2(-/-) mice. Expression of endothelin-1, a potent vasoconstrictor, was elevated in lungs of Lpar1(-/-)2(-/-) mice, and expression of endothelin(B) receptor, which promotes vasodilation and clears endothelin, was reduced in Enpp2(+/-) and Lpar1(-/-)2(-/-) mice.
conclusionsOur findings indicate that LPA may negatively regulate pulmonary vascular pressure through LPA(1) and LPA(2) receptors and that in the absence of LPA signaling, upregulation in the endothelin system favors remodeling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.