ArticleThe Journal of clinical investigation2022
Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Acute ST-Segment Elevation Myocardial Infarction Following Multimodality Cancer Therapy in a HER2-Positive Breast Cancer Patient: A Case Report.Journal of cardiovascular development and disease · 2026Article
- Burden of cardiovascular diseases in breast cancer survivors: a 9-year retrospective cohort study based on regional medical data in Inner Mongolia China.Cardio-oncology (London, England) · 2026Article
- Vascular Sphingosine Kinase 1 Regulates Angiotensin II-Induced Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Sympathetic Neural Overactivation, Vascular Dysfunction, and Exercise Intolerance in Long-Term Survivors of Breast Cancer Treated With Doxorubicin and Trastuzumab-Based Chemotherapy.Journal of the American Heart Association · 2026Article
- Sensor Monitoring of Thermal and Vascular Changes During Neoadjuvant Treatment.Sensors (Basel, Switzerland) · 2026Article
- Vascular Toxicities of Cancer Therapies: 2025 Update.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Doxorubicin-Induced Cardiac Remodeling: Mechanisms and Mitigation Strategies.Cardiovascular drugs and therapy · 2026Review
- Role of Perindopril in Mitigating Doxorubicin's Vascular Toxicity in a Rat Model.Cardiovascular toxicology · 2026Article
- Exosome-Related Gene Signature Predicts Prognosis and Immunotherapy in Gastric Cancer.International journal of genomics · 2026Article
- The mechanisms and therapeutic advances of interactions between breast cancer and cardiovascular diseases.Frontiers in pharmacology · 2026Review
- Sustained mesenchymal reprogramming of endothelial cells after completion of chemotherapy.Cardio-oncology (London, England) · 2025Article
- Pretreatment Circulating Vascular Biomarkers Predict Cancer Therapy-Related Cardiac Dysfunction During HER2JACC. CardioOncology · 2025Article
- Characterization of anticancer therapy-induced microvascular dysfunction in patients with breast cancer supports targeted intervention.JCI insight · 2025Article
- Deciphering key chemotherapeutic drug targets within tyrosine metabolism for breast cancer and advancing a wide-ranging diagnostic strategy.Discover oncology · 2025Article
- NOX4 serves as a pan-cancer prognostic biomarker and therapeutic target in tumorigenesis.Scientific reports · 2025Article
- Cardiotoxicity in Elderly Breast Cancer Patients.Cancers · 2025Review
- Neutrophil extracellular traps induced by neoadjuvant chemotherapy of breast cancer promotes vascular endothelial damage.Breast cancer research : BCR · 2025Article
- Reactive oxygen species in hypertension.Nature reviews. Cardiology · 2025Review
- Candesartan preserves aortic structure and function in cisplatin-treated rats by upregulating SIRT1/Nrf2/HO-1 signaling and suppressing oxidative stress, TLR-4/NF-κB signaling, and necroptosis.Frontiers in pharmacology · 2025Article
- Maternal high glucose and fat diet exposure impaired vascular constriction via miR-325-3P/SHIP2/NOX2 pathway axis in offspring vessels.Cellular and molecular life sciences : CMLS · 2024Article
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Authors and funding
28 authors at 9 institutions in 5 countries.
Funding
Abstract
Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.
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