Pharmacological and physiological response in Apoe<sup>−/−</sup> mice exposed to cigarette smoke or e-cigarette aerosols

Eden, Matthew; Farra, Yasmeen M; Matz, Jacob; Bellini, Chiara; Oakes, Jessica M.

doi:10.1080/08958378.2022.2086948

Cited by 10 publications

(15 citation statements)

References 83 publications

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“…Likewise, pathological mechanisms may modify the natural course of the aging process, supporting a multi-organ accelerated decay. Motivated by our interest in the superposition between aging and environmental pollutant inhalation 27,[34][35][36] , we probed cell makeup and gene/protein expression in tissues from the ascending thoracic aorta (ATA) of young and aged mice, to interpret the evolving geometrical features and functional metrics that this aortic segment exhibits throughout the mouse adult lifespan.…”

Section: Discussionmentioning

confidence: 99%

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Farra

Rivera

Silvestro

et al. 2022

Preprint

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Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic (ATA) compared to distal segments of the aorta and that tissues in both the medial and adventitial compartments of the ATA stiffen during aging. Single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T-lymphocytes accumulate in the adventitia and likely promote fibrosis, while activation of mechanosensitive piezo-1 enhances medial vasoconstriction. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

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Section: Discussionmentioning

confidence: 99%

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Farra

Rivera

Silvestro

et al. 2022

Preprint

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“…14 Although direct measurement of particle deposition and clearance remain challenging to date, dosimetry models that couple airflow simulations with particle transport facilitate prediction of regional deposition fractions. 122,[124][125][126] As an additional benefit, these computational tools enable incorporation of processes for particle transport, deposition, and clearance that are tailored to each species and, therefore, remain instrumental in establishing equivalent exposure conditions between animals and humans.…”

Section: Compendium On Environmental Impacts On Cardiovascular Health...mentioning

confidence: 99%

Impact of Wildfires on Cardiovascular Health

Williams,

Perreault,

Yazbeck

et al. 2024

Circulation Research

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Wildfire smoke (WFS) is a mixture of respirable particulate matter, environmental gases, and other hazardous pollutants that originate from the unplanned burning of arid vegetation during wildfires. The increasing size and frequency of recent wildfires has escalated public and occupational health concerns regarding WFS inhalation, by either individuals living nearby and downstream an active fire or wildland firefighters and other workers that face unavoidable exposure because of their profession. In this review, we first synthesize current evidence from environmental, controlled, and interventional human exposure studies, to highlight positive associations between WFS inhalation and cardiovascular morbidity and mortality. Motivated by these findings, we discuss preventative measures and suggest interventions to mitigate the cardiovascular impact of wildfires. We then review animal and cell exposure studies to call attention on the pathophysiological processes that support the deterioration of cardiovascular tissues and organs in response to WFS inhalation. Acknowledging the challenges of integrating evidence across independent sources, we contextualize laboratory-scale exposure approaches according to the biological processes that they model and offer suggestions for ensuring relevance to the human condition. Noting that wildfires are significant contributors to ambient air pollution, we compare the biological responses triggered by WFS to those of other harmful pollutants. We also review evidence for how WFS inhalation may trigger mechanisms that have been proposed as mediators of adverse cardiovascular effects upon exposure to air pollution. We finally conclude by highlighting research areas that demand further consideration. Overall, we aspire for this work to serve as a catalyst for regulatory initiatives to mitigate the adverse cardiovascular effects of WFS inhalation in the community and alleviate the occupational risk in wildland firefighters.

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“…We have recently shown that e-cigarette devices emit levels of fine and ultra-fine particulate matter comparable to those found in cigarette smoke. 12 Also similar to cigarette smoke, e-cigarette aerosol contains irritant aldehydes such as acrolein, free radicals, metals, and other chemicals that are harmful to human health. 5, 13, 14, 15 While nervous system signaling due to airway irritation has been implicated in the immediate vascular response to inhaled smoke or aerosol, 16 deposition of respirable particles into the deep lungs otherwise mediates the long-term outcomes.…”

Section: Introductionmentioning

confidence: 99%

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

Farra,

Matz,

Wilker

et al. 2024

Preprint

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ObjectiveElectronic (e-)cigarettes are the most used tobacco product amongst youth, and adult smokers favor e-cigarettes over approved cessations aids. Despite the lower perceived harm of vaping compared to smoking, inhalation of e-cigarette aerosol elicits cardiovascular responses that may lead to permanent injury when repeated over time. We thus aimed to infer the long-term outcomes of vaping on the function and structure of the aorta and shed light on the underlying cellular and molecular mechanisms.Approach and ResultsWe exposed female hypercholesterolemic mice to either pod-mod e-cigarette aerosol or room air daily for 24 weeks. Chronic inhalation of e-cigarette aerosol triggered accumulation of inflam-matory signals systemically and within aortic tissues, as well as T lymphocyte accrual in the aortic wall. Reduced eNOS expression and enhanced ROS production following eNOS uncoupling and NADPH oxi-dase activation curbed nitric oxide availability in the aorta of mice exposed to e-cigarette aerosol, impairing the endothelium-dependent vasodilatation that regulates blood flow distribution. Inhalation of e-cigarette aerosol thickened and stiffened aortic tissues via collagen deposition and remodeling, hindering the storage of elastic energy and limiting the cyclic distensibility that enables the aorta to function as a pressure reservoir. These effects combined contributed to raising systolic and pulse pressure above control levels.ConclusionsChronic inhalation of aerosol from pod-mod e-cigarettes promotes oxidative stress, inflammation, and fibrosis within aortic tissues, significantly impairing passive and vasoactive aortic functions. This evidence provides new insights on the biological processes that increase the risk for adverse cardio-vascular events as a result of pod-mod e-cigarette vaping.

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Pharmacological and physiological response in Apoe^−/− mice exposed to cigarette smoke or e-cigarette aerosols

Cited by 10 publications

References 83 publications

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Impact of Wildfires on Cardiovascular Health

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

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Pharmacological and physiological response in Apoe−/− mice exposed to cigarette smoke or e-cigarette aerosols

Cited by 10 publications

References 83 publications

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Impact of Wildfires on Cardiovascular Health

Chronic Pod-Mod E-Cigarette Aerosol Exposure Induces Aortic Dysfunction in Hypercholesterolemic Mice: Role of Oxidative Stress and Inflammation

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Pharmacological and physiological response in Apoe^−/− mice exposed to cigarette smoke or e-cigarette aerosols