ArticleThe Journal of clinical investigation2024
RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Autophagy-Targeted Vascular Remodeling in Pulmonary Arterial Hypertension: Molecular Mechanisms and Therapeutic Perspectives.Journal of cardiovascular development and disease · 2026Review
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2026Article
- Loss of ROR2 Tyrosine Kinase Receptor Is Associated With Endothelial Dysfunction in PAH via Inappropriate Integrin β1 Activation.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions.Cell proliferation · 2026Review
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Defect in lysosomal enzyme trafficking and sorting is associated with irreversibility of pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2026Article
- Construction of an early diagnostic model for pulmonary hypertension based on aging-related signature genes and identification of potential therapeutic targets.Scientific reports · 2025Article
- Cellular and molecular mechanisms underlying cardiovascular aging.Cellular & molecular biology letters · 2025Review
- Integrative proteomics and metabolomics analyses reveals the regulation of autophagy and ferroptosis by RAB10 through Slc37a2/mTOR pathway in breast cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- USP4 depletion-driven RAB7A ubiquitylation impairs autophagosome-lysosome fusion and aggravates periodontitis.Autophagy · 2025Article
- Specialized Pulmonary Vascular Cells in Development and Disease.Annual review of physiology · 2025Review
- Interaction of ferroptosis and cuproptosis in the perspective of pulmonary hypertension.Frontiers in cardiovascular medicine · 2025Review
- Caffeine, MitoQ, and GABA Prophylaxis of Mitochondrial Dysfunction Induced in Human Pulmonary Cells by Normobaric-Hyperoxia and Hyperbaric-Hyperoxia.Oxidative medicine and cellular longevity · 2025Article
- RAB7 protects against ischemic heart failure via promoting non-canonical TUFM mitophagy pathway.Theranostics · 2025Article
- Unlocking the secrets of glucose metabolism reprogramming: the role in pulmonary diseases.Frontiers in pharmacology · 2025Review
- Lipocalin-2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension.Cell proliferation · 2024Article
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20 authors at 8 institutions in 2 countries.
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Abstract
Pulmonary arterial hypertension (PAH) is a devastating and progressive disease with limited treatment options. Endothelial dysfunction plays a central role in the development and progression of PAH, yet the underlying mechanisms are incompletely understood. The endosome-lysosome system is important to maintain cellular health, and the small GTPase RAB7 regulates many functions of this system. Here, we explored the role of RAB7 in endothelial cell (EC) function and lung vascular homeostasis. We found reduced expression of RAB7 in ECs from patients with PAH. Endothelial haploinsufficiency of RAB7 caused spontaneous pulmonary hypertension (PH) in mice. Silencing of RAB7 in ECs induced broad changes in gene expression revealed via RNA-Seq, and RAB7-silenced ECs showed impaired angiogenesis and expansion of a senescent cell fraction, combined with impaired endolysosomal trafficking and degradation, suggesting inhibition of autophagy at the predegradation level. Furthermore, mitochondrial membrane potential and oxidative phosphorylation were decreased, and glycolysis was enhanced. Treatment with the RAB7 activator ML-098 reduced established PH in rats with chronic hypoxia/SU5416. In conclusion, we demonstrate for the first time to our knowledge the fundamental impairment of EC function by loss of RAB7, causing PH, and show RAB7 activation to be a potential therapeutic strategy in a preclinical model of 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.