ArticleCardiovascular research2013
Aquaporin 1, Nox1, and Ask1 mediate oxidant-induced smooth muscle cell hypertrophy.
Article in Cardiovascular research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Leiomodin 1 deficiency promotes lipid accumulation and redirects gene regulatory programs in smooth muscle cells exposed to oxidized LDL.Research square · 2026Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Aquaporin 1 confers apoptosis resistance in pulmonary arterial smooth muscle cells from the SU5416 hypoxia rat model.Physiological reports · 2024Article
- Vascular Inflammation and Smooth Muscle Contractility: The Role of Nox1-Derived Superoxide and LRRC8 Anion Channels.Hypertension (Dallas, Tex. : 1979) · 2024Review
- A novel aquaporin Aagp contributes toVirulence · 2023Article
- Extracellular SOD modulates canonical TNFα signaling and α5β1 integrin transactivation in vascular smooth muscle cells.Free radical biology & medicine · 2023Article
- Relevant Membrane Transport Proteins as Possible Gatekeepers for Effective Pharmacological Ascorbate Treatment in Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Novel and Converging Ways of NOX2 and SOD3 in Trafficking and Redox Signaling in Macrophages.Antioxidants (Basel, Switzerland) · 2021Review
- TNFα and Reactive Oxygen Signaling in Vascular Smooth Muscle Cells in Hypertension and Atherosclerosis.American journal of hypertension · 2020Review
- Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue.Antioxidants (Basel, Switzerland) · 2020Review
- Endothelial dysfunction in neuroprogressive disorders-causes and suggested treatments.BMC medicine · 2020Review
- Redox regulation of nitrosyl-hemoglobin in human erythrocytes.Redox biology · 2020Article
- Hydrogen peroxide in the ER: A tale of triage.Redox biology · 2020Article
- Prokaryotic Aquaporins.Cells · 2019Review
- Lipid peroxidation increases hydrogen peroxide permeability leading to cell death in cancer cell lines that lack mtDNA.Cancer science · 2019Article
- Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis.American journal of physiology. Heart and circulatory physiology · 2019Article
- AThe Journal of biological chemistry · 2019Article
- Peroxiporins in Cancer.International journal of molecular sciences · 2019Review
- Lipid Profile and Aquaporin Expression under Oxidative Stress in Breast Cancer Cells of Different Malignancies.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
Abstract
aimsReactive oxygen species (ROS)-mediated intracellular signalling is well described in the vasculature, yet the precise roles of ROS in paracrine signalling are not known. Studies implicate interstitial ROS hydrogen peroxide (H(2)O(2)) in vascular disease, and plasma H(2)O(2) levels in the micromolar range are detectable in animal models and humans with hypertension. Recently, H(2)O(2) was shown to cross biological membranes of non-vascular cells via aquaporin (Aqp) water channels. Previous findings suggest that H(2)O(2) activates NADPH oxidase (Nox) enzymes in vascular cells and apoptosis signal-regulating kinase 1 (Ask1) in non-vascular cells. We hypothesized that extracellular H(2)O(2) induces smooth muscle cell (SMC) hypertrophy by a mechanism involving Aqp1, Nox1, and Ask1. METHODS AND
resultsTreatment of rat aortic SMCs (rASMC) with exogenous H(2)O(2) resulted in a concentration-dependent increase in Nox-derived superoxide (O(2)(•-)), determined by L-012 chemiluminescence, cytochrome c and electron paramagnetic resonance. Nox1 was verified as the source of O(2)(·-) by siRNA. Aqp1 siRNA attenuated H(2)O(2) cellular entry and H(2)O(2)-induced O(2)(•-) production. H(2)O(2) treatment increased Ask1 activation and induced rASMC hypertrophy in a Nox1-dependent mechanism. Adenoviral-dominant-negative Ask1 attenuated H(2)O(2)-induced rASMC hypertrophy and adenoviral overexpression of Ask1 augmented it.
conclusionOur results demonstrate for the first time that extracellular H(2)O(2), at pathophysiological concentrations, stimulates rASMC Nox1-derived O(2)(•-), subsequent Ask1 activation and SMC hypertrophy. The data demonstrate a novel pathway by which H(2)O(2) enters vascular cells via aquaporins and activates Nox, leading to hypertrophy, and provide multiple novel targets for combinatorial therapeutics development targeting hypertrophy and vascular disease.
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