Nicotine promotes vascular calcification via intracellular Ca2+-mediated, Nox5-induced oxidative stress, and extracellular vesicle release in vascular smooth muscle cells
| Autor: | Sebastian Reith, Brecht A. G. Willems, Michael J. Jacobs, Elham Bidar, Barend Mees, Ehsan Natour, Nadina Stadler, Nikolaus Marx, Malgorzata Furmanik, Mathias Burgmaier, Kathrin Burgmaier, Sylvia Heeneman, Leon J. Schurgers, Ploingarm Petsophonsakul, Florian Kahles, Chris P. M. Reutelingsperger, Felix Gremse |
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| Přispěvatelé: | RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, Biochemie, Pathologie, RS: Carim - B07 The vulnerable plaque: makers and markers, MUMC+: MA Med Staf Spec CTC (9), RS: Carim - V04 Surgical intervention, CTC, MUMC+: Hart en Vaat Centrum (3), RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, MUMC+: *HVC European Venous Centre (9), Vascular Surgery, MUMC+: MA Vaatchirurgie CVC (3), MUMC+: MA Med Staf Spec Vaatchirurgie (9) |
| Rok vydání: | 2021 |
| Předmět: |
CORONARY-ARTERY CALCIFICATION
0301 basic medicine Nicotine medicine.medical_specialty Vascular smooth muscle CALCIUM-PHOSPHATE Physiology Myocytes Smooth Muscle 030204 cardiovascular system & hematology SUBCLINICAL ATHEROSCLEROSIS UP-REGULATION medicine.disease_cause Muscle Smooth Vascular Extracellular Vesicles 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine AORTIC-ANEURYSMS medicine Humans Secretion FETUIN-A VITAMIN-K Vascular Calcification Cells Cultured Chemistry NECROSIS-FACTOR-ALPHA X-Ray Microtomography Extracellular vesicle Atherosclerosis medicine.disease Oxidative Stress Nicotinic acetylcholine receptor 030104 developmental biology Endocrinology NADPH Oxidase 5 Nicotine Vascular calcification Vascular smooth muscle cell phenotypic switching Nox5 Vitamin K2 CARDIOVASCULAR-DISEASE Cardiovascular Diseases Calcium CIGARETTE-SMOKING Cardiology and Cardiovascular Medicine Intracellular Oxidative stress Calcification medicine.drug |
| Zdroj: | Cardiovascular research 118(9), 2196-2210 (2022). doi:10.1093/cvr/cvab244 Cardiovascular Research, 118(9), 2196-2210. Oxford University Press |
| ISSN: | 1755-3245 0008-6363 |
| Popis: | Aims Smokers are at increased risk of cardiovascular events. However, the exact mechanisms through which smoking influences cardiovascular disease resulting in accelerated atherosclerosis and vascular calcification are unknown. The aim of this study was to investigate effects of nicotine on initiation of vascular smooth muscle cell (VSMC) calcification and to elucidate underlying mechanisms. Methods and results We assessed vascular calcification of 62 carotid lesions of both smoking and non-smoking patients using ex vivo micro-computed tomography (µCT) scanning. Calcification was present more often in carotid plaques of smokers (n = 22 of 30, 73.3%) compared to non-smokers (n = 11 of 32, 34.3%; P Conclusion In this study, we provide evidence that nicotine induces Nox5-mediated pro-calcific processes as novel mechanism of increased atherosclerotic calcification. We identified that activation of α7 and α3 nAChR by nicotine increases intracellular Ca2+ and initiates calcification of hVSMCs through increased Nox5 activity, leading to oxidative stress-mediated EV release. Identifying the role of Nox5-induced oxidative stress opens novel avenues for diagnosis and treatment of smoking-induced cardiovascular disease. |
| Databáze: | OpenAIRE |
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