Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity
| العنوان: | Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity |
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| المؤلفون: | Timen J. Schenk, Wim Martinet, Kasper Favere, Birgit Van Asbroeck, Dustin N. Krüger, Emeline M. Van Craenenbroeck, Callan D. Wesley, Owen R. Diebels, Guido R.Y. De Meyer, Matthias Bosman, Cédric H. G. Neutel, Pieter-Jan Guns, Bart Faes |
| المصدر: | International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12812 International Journal of Molecular Sciences INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES International journal of molecular sciences International Journal of Molecular Sciences, Vol 22, Iss 12812, p 12812 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Contraction (grammar), Vascular smooth muscle, cardio-oncology, Vasodilation, Pharmacology, Muscle, Smooth, Vascular, endothelial dysfunction, Mice, Medicine and Health Sciences, polycyclic compounds, Diltiazem, Biology (General), Spectroscopy, Antibiotics, Antineoplastic, Chemistry, General Medicine, Computer Science Applications, arterial stiffness, medicine.drug, Muscle Contraction, QH301-705.5, macromolecular substances, doxorubicin, Catalysis, Article, Inorganic Chemistry, Vascular Stiffness, In vivo, medicine, Animals, Physical and Theoretical Chemistry, QD1-999, Biology, Molecular Biology, Phenylephrine, organic chemicals, Organic Chemistry, technology, industry, and agriculture, Biology and Life Sciences, Angiotensin II, vascular smooth muscle cell contraction, Mice, Inbred C57BL, carbohydrates (lipids), Vasoconstriction, Calcium, non-selective cation channel, Calcium Channels, Endothelium, Vascular, Ex vivo |
| الوصف: | Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca2+ release from the sarcoplasmic reticulum (0 mM Ca2+), but it reduced the subsequent tonic phase characterised by Ca2+ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca2+ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K+ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms222312812 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::886c3ba8b9ce92548218e0d3d99a03fcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....886c3ba8b9ce92548218e0d3d99a03fc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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| DOI: | 10.3390/ijms222312812 |