ArticleMolecular medicine (Cambridge, Mass.)2024
HIF-1α mediates hypertension and vascular remodeling in sleep apnea via hippo-YAP pathway activation.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.Journal of applied genetics · 2026Review
- Review
- Gemcitabine activates the Hippo signaling pathway and suppresses tumor growth by stabilizing large tumor suppressor kinase 2 through the hypoxia-inducible factor 1-alpha/ubiquitin protein ligase E3 component N-recognin 5 axis.Journal of cell communication and signaling · 2026Article
- Mild Cognitive Impairment Associated with Obstructive Sleep Apnoea: A Pilot Study on Oxygen-Related Plasma Biomarkers and Network Analysis.Molecular neurobiology · 2026Article
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Mechanisms underlying end-organ injury in sleep apnoea.The European respiratory journal · 2026Review
- Impacts of obstructive sleep apnea on collateral circulation in stroke patients with proximal middle cerebral artery stenosis or occlusion.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- MicroRNA-320а as a novel biomarker at preclinical stage of necrotizing enterocolitis in term neonates with congenital heart defects.World journal of clinical pediatrics · 2025Article
- Oxidative Stress and Inflammation in Hypoxemic Respiratory Diseases and Their Comorbidities: Molecular Insights and Diagnostic Advances in Chronic Obstructive Pulmonary Disease and Sleep Apnea.Antioxidants (Basel, Switzerland) · 2025Review
- Selenomethionine inhibits the proliferation of hypoxia-induced pulmonary artery smooth muscle cells by inhibiting ROS and HIF-1α-ACE-AngII axis.Scientific reports · 2025Article
- Hypoxia Regulates the Proliferation and Apoptosis of Coronary Artery Smooth Muscle Cells Through HIF-1α Mediated Autophagy in Yak.Biomolecules · 2025Article
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9 authors.
Funding
Abstract
backgroundSleep apnea syndrome (SAS) is associated with hypertension and vascular remodeling. Hypoxia-inducible factor-1α (HIF-1α) and the Hippo-YAP pathway are implicated in these processes, but their specific roles remain unclear. This study investigated the HIF-1α/Hippo-YAP pathway in SAS-related hypertension.
methodsWe established a rat model of SAS-induced hypertension via chronic intermittent hypoxia (CIH). Rats were treated with siRNA targeting HIF-1α. Blood pressure, inflammation, oxidative stress, vascular remodeling, and VSMC function were assessed. In vitro experiments with A7r5 cells and human aortic smooth muscle cells (HAoSMCs) explored the effects of HIF-1α silencing and YAP1 overexpression.
resultsCompared with the control group, the CIH group presented significant increases in both HIF-1α and YAP1 expression, which correlated with increased blood pressure and vascular changes. HIF-1α silencing reduced hypertension, oxidative stress, inflammation, and the severity of vascular remodeling. Specifically, siRNA treatment for HIF-1α normalized blood pressure, decreased the levels of oxidative damage markers (increased SOD and decreased MDA), and reversed the changes in the levels of inflammatory markers (decreased high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and soluble E-selectin (sE-s)). Structural analyses revealed reduced vascular smooth muscle cell proliferation and collagen deposition, along with normalization of cellular markers, such as α-SMA and TGF-β1. Furthermore, the Hippo-YAP pathway appeared to mediate these effects, as evidenced by altered YAP1 expression and activity upon HIF-1α modulation.
conclusionsOur findings demonstrate the significance of the HIF-1α/Hippo-YAP pathway in CIH-induced hypertension and vascular remodeling. HIF-1α contributes to these pathophysiological processes by promoting oxidative stress, inflammation, and aberrant VSMC behavior. Targeting this pathway could offer new therapeutic strategies for CIH-related cardiovascular complications in SAS patients.
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