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Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration

View ORCID ProfileAlejandra P. Garza, View ORCID ProfileLorena Morton, View ORCID ProfileÉva Pállinger, View ORCID ProfileEdit I. Buzás, View ORCID ProfileStefanie Schreiber, View ORCID ProfileBjörn H. Schott, View ORCID ProfileIldiko Rita Dunay
doi: https://doi.org/10.1101/2022.09.27.509833
Alejandra P. Garza
1Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany
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Lorena Morton
1Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany
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Éva Pállinger
2Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
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Edit I. Buzás
2Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest
3HCEMM SU Extracellular Vesicle Research Group, Budapest
4ELKH-SE Translational Extracellular Vesicle Research Group, Budapest
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Stefanie Schreiber
5Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany
6Center for Behavioral Brain Sciences, Magdeburg, Germany
7German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Björn H. Schott
6Center for Behavioral Brain Sciences, Magdeburg, Germany
7German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
8Leibniz Institute of Neurobiology, Magdeburg, Germany
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Ildiko Rita Dunay
1Institute of Inflammation and Neurodegeneration, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany
6Center for Behavioral Brain Sciences, Magdeburg, Germany
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  • For correspondence: ildiko.dunay@med.ovgu.de
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Abstract

Tobacco smoking is strongly linked to vascular damage contributing to the development of hypertension, atherosclerosis, as well as an increased risk for neurodegeneration. Still, the contribution of the innate immune system to the development of vascular damage upon chronic tobacco use before the onset of clinical symptoms is not fully elucidated. Notably, our data provide evidence that a single acute exposure to tobacco in never smokers elicits a secretion of extracellular vesicles by endothelial cells expressing CD105 and CD49e, granting further recognition of early preclinical biomarker of vascular damage. Further, we investigated the effects of smoking on the immune system of healthy asymptomatic chronic smokers compared to never-smokers and focused on the innate immune system. Our data reveal a distinct immune landscape representative for early stages of vascular damage before tobacco smoking related disease develop in clinically asymptomatic chronic smokers. These results indicate a dysregulated immuno-vascular axis in chronic tobacco smokers that are considered healthy individuals. The distinct alterations are characterized by increased CD36 expression by blood monocyte subsets, neutrophilia, increased plasma IL-18 and reduced levels of IL-33, IL-10 and IL-8. Further, the detection of lower circulating BDNF and elevated sTREM2, specific markers for neurodegeneration, suggests a considerable pre-clinical impact of tobacco smoking on CNS function in clinically healthy individuals. These findings provide further insight into the initial and ongoing effects of tobacco smoking and the potential vascular damage contributing to the progression of neurodegenerative disorders, specifically cerebrovascular dysfunction and dementia.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 28, 2022.
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Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration
Alejandra P. Garza, Lorena Morton, Éva Pállinger, Edit I. Buzás, Stefanie Schreiber, Björn H. Schott, Ildiko Rita Dunay
bioRxiv 2022.09.27.509833; doi: https://doi.org/10.1101/2022.09.27.509833
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Initial and ongoing tobacco smoking elicits vascular damage and distinct inflammatory response linked to neurodegeneration
Alejandra P. Garza, Lorena Morton, Éva Pállinger, Edit I. Buzás, Stefanie Schreiber, Björn H. Schott, Ildiko Rita Dunay
bioRxiv 2022.09.27.509833; doi: https://doi.org/10.1101/2022.09.27.509833

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