ArticleArteriosclerosis, thrombosis, and vascular biology2015
Endothelial uncoupling protein 2 regulates mitophagy and pulmonary hypertension during intermittent hypoxia.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 118 citations in OpenAlex.
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Advances in understanding mitophagy's role in lung injury.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2026Review
- Mitochondrial acid-sensing ion channel 1a deficiency induces mitochondrial dysfunction in pulmonary arterial smooth muscle cells.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Mitochondria-associated endoplasmic reticulum membranes: Emerging regulators of cardiac microvascular ischemia/reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- PINK1/Parkin Deficiency Enhances Vascular Remodeling and Aggravates Hypoxia-induced Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- 2-Methoxyestradiol attenuates lung injury induced by chronic intermittent hypoxia via inhibiting the HIF1-α/SLC7A11 pathway.Scientific reports · 2025Article
- Hyperuricemia Facilitates Uric Acid-Mediated Vascular Endothelial Cell Damage by Inhibiting Mitophagy.Cell biochemistry and biophysics · 2025Article
- Emerging insights into pulmonary hypertension: the potential role of mitochondrial dysfunction and redox homeostasis.Molecular and cellular biochemistry · 2025Review
- Multidimensional study on mitochondrial dysfunction in pulmonary hypertension.Frontiers in medicine · 2025Review
- Emerging role and the signaling pathways of uncoupling protein 2 in kidney diseases.Renal failure · 2024Review
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension.The Journal of clinical investigation · 2024Article
- Metabolic reprogramming, oxidative stress, and pulmonary hypertension.Redox biology · 2023Review
- PDK1 upregulates PINK1-mediated pulmonary endothelial cell mitophagy during hypoxia-induced pulmonary vascular remodeling.Molecular biology reports · 2023Article
- Emerging role of mitophagy in heart failure: from molecular mechanism to targeted therapy.Cell cycle (Georgetown, Tex.) · 2023Review
- Autophagy impairment in patients with obstructive sleep apnea modulates intermittent hypoxia-induced oxidative stress and cell apoptosis via hypermethylation of the ATG5 gene promoter region.European journal of medical research · 2023Article
- Mitochondria in hypoxic pulmonary hypertension, roles and the potential targets.Frontiers in physiology · 2023Review
- SUMOylation targeting mitophagy in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Neonatal intermittent hypoxia persistently impairs lung vascular development and induces long-term lung mitochondrial DNA damage.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
objectivesPulmonary hypertension (PH) is a process of lung vascular remodeling, which can lead to right heart dysfunction and significant morbidity. The underlying mechanisms leading to PH are not well understood, and therapies are limited. Using intermittent hypoxia (IH) as a model of oxidant-induced PH, we identified an important role for endothelial cell mitophagy via mitochondrial uncoupling protein 2 (Ucp2) in the development of IH-induced PH. APPROACH AND
resultsUcp2 endothelial knockout (VE-KO) and Ucp2 Flox (Flox) mice were subjected to 5 weeks of IH. Ucp2 VE-KO mice exhibited higher right ventricular systolic pressure and worse right heart hypertrophy, as measured by increased right ventricle weight/left ventricle plus septal weight (RV/LV+S) ratio, at baseline and after IH. These changes were accompanied by increased mitophagy. Primary mouse lung endothelial cells transfected with Ucp2 siRNA and subjected to cyclic exposures to CoCl2 (chemical hypoxia) showed increased mitophagy, as measured by PTEN-induced putative kinase 1 and LC3BII/I ratios, decreased mitochondrial biogenesis, and increased apoptosis. Similar results were obtained in primary lung endothelial cells isolated from VE-KO mice. Moreover, silencing PTEN-induced putative kinase 1 in the endothelium of Ucp2 knockout mice, using endothelial-targeted lentiviral silencing RNA in vivo, prevented IH-induced PH. Human pulmonary artery endothelial cells from people with PH demonstrated changes similar to Ucp2-silenced mouse lung endothelial cells.
conclusionsThe loss of endothelial Ucp2 leads to excessive PTEN-induced putative kinase 1-induced mitophagy, inadequate mitochondrial biosynthesis, and increased apoptosis in endothelium. An endothelial Ucp2-PTEN-induced putative kinase 1 axis may be effective therapeutic targets in PH.
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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.