ArticleRespiratory research2023
Inhibition of Hsp110-STAT3 interaction in endothelial cells alleviates vascular remodeling in hypoxic pulmonary arterial Hypertension model.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Predictors of Recurrence Following Bronchial Artery Embolisation (BAE) for Haemoptysis: A Systematic Review and Evidence Synthesis Analyses Using SWiM Guidelines.Cardiovascular and interventional radiology · 2026Pooled it
- The Research Progress in Targeted Therapy for Hypertension via Heat Shock Proteins.International journal of molecular sciences · 2026Review
- Article
- Hypoxic Pulmonary Hypertension: Molecular Mechanisms and Clinical Research Advances.International journal of molecular sciences · 2026Review
- Mesenchymal stromal cells alleviate pulmonary arterial hypertension by suppressing pulmonary arterial adventitial fibroblast activation and extracellular matrix remodeling via the SOCS3/STAT3 pathway.Stem cell research & therapy · 2026Article
- Multifaceted mechanisms of plant metabolites in pulmonary arterial hypertension: a critical review beyond vasodilation.Frontiers in pharmacology · 2026Review
- TRAF6 promotes pulmonary hypertension by enhancing K63-linked ubiquitination and activation of STAT3.Frontiers in pharmacology · 2026Article
- Nobiletin alleviates hypoxia-induced pulmonary hypertension by inhibiting calcium-sensing receptor.Journal of natural medicines · 2025Article
- Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- GSDME in cardiovascular diseases: research system and contemporary progress.Frontiers in immunology · 2025Review
- Bioactive compound combinations fromFrontiers in pharmacology · 2025Article
- Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.Drug design, development and therapy · 2024Article
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9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundPulmonary arterial hypertension (PAH) is a progressive and devastating disease characterized by pulmonary vascular remodeling which is associated with the malignant phenotypes of pulmonary vascular cells. Recently, the effects of heat shock protein 110 (Hsp110) in human arterial smooth muscle cells were reported. However, the underlying roles and mechanisms of Hsp110 in human pulmonary arterial endothelial cells (HPAECs) that was disordered firstly at the early stage of PAH remain unknown.
methodsIn this research, the expression of Hsp110 in PAH human patients and rat models was investigated, and the Hsp110 localization was determined both in vivo and in vitro. The roles and mechanism of elevated Hsp110 in excessive cell proliferation and migration of HPAECs were assessed respectively exposed to hypoxia. Small molecule inhibitors targeting Hsp110-STAT3 interaction were screened via fluorescence polarization, anti-aggregation and western blot assays. Moreover, the effects of compound 6 on HPAECs abnormal phenotypes in vitro and pulmonary vascular remodeling of hypoxia-indued PAH rats in vivo by interrupting Hsp110-STAT3 interaction were evaluated.
resultsOur studies demonstrated that Hsp110 expression was increased in the serum of patients with PAH, as well as in the lungs and pulmonary arteries of PAH rats, when compared to their respective healthy subjects. Moreover, Hsp110 levels were significantly elevated in HPAECs under hypoxia and mediated its aberrant phenotypes. Furthermore, boosted Hsp110-STAT3 interaction resulted in abnormal proliferation and migration via elevating p-STAT3 and c-Myc in HPAECs. Notably, we successfully identified compound 6 as potent Hsp110-STAT3 interaction inhibitor, which effectively inhibited HPAECs proliferation and migration, and significantly ameliorated right heart hypertrophy and vascular remodeling of rats with PAH.
conclusionsOur studies suggest that elevated Hsp110 plays a vital role in HPAECs and inhibition of the Hsp110-STAT3 interaction is a novel strategy for improving vascular remodeling. In addition, compound 6 could serve as a promising lead compound for developing first-in-class drugs against PAH.
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