ArticlePhysiological genomics2009
Effect of PPARgamma inhibition on pulmonary endothelial cell gene expression: gene profiling in pulmonary hypertension.
Article in Physiological genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01825369 (Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow), which is not on this map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow
Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling.International journal of molecular sciences · 2023Article
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- Cardiovascular Effects Mediated by HMMR and CD44.Mediators of inflammation · 2021Review
- Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- PPARγ Regulates Mitochondrial Structure and Function and Human Pulmonary Artery Smooth Muscle Cell Proliferation.American journal of respiratory cell and molecular biology · 2018Article
- Pharmacological activation of PPARγ inhibits hypoxia-induced proliferation through a caveolin-1-targeted and -dependent mechanism in PASMCs.American journal of physiology. Cell physiology · 2018Article
- Egr-1 mediates leptin-induced PPARγ reduction and proliferation of pulmonary artery smooth muscle cells.Molecular biology of the cell · 2018Article
- PPARγ attenuates hypoxia-induced hypertrophic transcriptional pathways in the heart.Pulmonary circulation · 2017Article
- Time-dependent PPARγ Modulation of HIF-1α Signaling in Hypoxic Pulmonary Artery Smooth Muscle Cells.The American journal of the medical sciences · 2016Article
- Inhibition of fatty acid synthase is protective in pulmonary hypertension.British journal of pharmacology · 2016Article
- Modulation of host ubiquitin system genes in human endometrial cell line infected with Mycobacterium tuberculosis.Medical microbiology and immunology · 2016Article
- PPAR Gamma and Angiogenesis: Endothelial Cells Perspective.Journal of diabetes research · 2016Review
- Peroxisome Proliferator-Activated Receptor γ-Mediated Inhibition on Hypoxia-Triggered Store-Operated Calcium Entry. A Caveolin-1-Dependent Mechanism.American journal of respiratory cell and molecular biology · 2015Article
- Enhanced caveolin-1 expression in smooth muscle cells: Possible prelude to neointima formation.World journal of cardiology · 2015Article
- PPARγ Ligands Attenuate Hypoxia-Induced Proliferation in Human Pulmonary Artery Smooth Muscle Cells through Modulation of MicroRNA-21.PloS one · 2015Article
- Pulmonary hypertension and metabolic syndrome: Possible connection, PPARγ and Caveolin-1.World journal of cardiology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Peroxisome proliferator-activated receptor type gamma (PPARgamma) is a subgroup of the PPAR transcription factor family. Recent studies indicate that loss of PPARgamma is associated with the development of pulmonary hypertension (PH). We hypothesized that the endothelial dysfunction associated with PPARgamma inhibition may play an important role in the disease process by altering cellular gene expression and signaling cascades. We utilized microarray analysis to determine if PPARgamma inhibition induced changes in gene expression in pulmonary arterial endothelial cells (PAEC). We identified 100 genes and expressed sequence tags (ESTs) that were upregulated by >1.5-fold and 21 genes and ESTs that were downregulated by >1.3-fold (P < 0.05) by PPARgamma inhibition. The upregulated genes can be broadly classified into four functional groups: cell cycle, angiogenesis, ubiquitin system, and zinc finger proteins. The genes with the highest fold change in expression: hyaluronan-mediated motility receptor (HMMR), VEGF receptor 2 (Flk-1), endothelial PAS domain protein 1 (EPAS1), basic fibroblast growth factor (FGF-2), and caveolin-1 in PAEC were validated by real time RT-PCR. We further validated the upregulation of HMMR, Flk-1, FGF2, and caveolin-1 by Western blot analysis. In keeping with the microarray results, PPARgamma inhibition led to re-entry of cell cycle at G(1)/S phase and cyclin C upregulation. PPARgamma inhibition also exacerbated VEGF-induced endothelial barrier disruption. Finally we confirmed the downregulation of PPARgamma and the upregulation of HMMR, Flk-1, FGF2, and Cav-1 proteins in the peripheral lung tissues of an ovine model of PH. In conclusion, we have identified an array of endothelial genes modulated by attenuated PPARgamma signaling that may play important roles in the development of PH.
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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.