Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology

Kunovac, Amina; Hathaway, Quincy A.; Pinti, Mark V.; Taylor, Andrew; Hollander, John M.

doi:10.1152/ajpheart.00026.2020

Cited by 22 publications

(10 citation statements)

References 180 publications

(255 reference statements)

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“…The application of broad-scale sequencing and “omics” approaches have been used in studies examining the health effects of air toxicants [ 25 – 27 ]. Specifically, transcriptomics provides a useful tool to determine the immediate adaptation, or maladaptation, after a stimulus.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction

et al. 2021

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Background Air pollution is a complex mixture of particles and gases, yet current regulations are based on single toxicant levels failing to consider potential interactive outcomes of co-exposures. We examined transcriptomic changes after inhalation co-exposure to a particulate and a gaseous component of air pollution and hypothesized that co-exposure would induce significantly greater impairments to mitochondrial bioenergetics. A whole-body inhalation exposure to ultrafine carbon black (CB), and ozone (O3) was performed, and the impact of single and multiple exposures was studied at relevant deposition levels. C57BL/6 mice were exposed to CB (10 mg/m3) and/or O3 (2 ppm) for 3 h (either a single exposure or four independent exposures). RNA was isolated from lungs and mRNA sequencing performed using the Illumina HiSeq. Lung pathology was evaluated by histology and immunohistochemistry. Electron transport chain (ETC) activities, electron flow, hydrogen peroxide production, and ATP content were assessed. Results Compared to individual exposure groups, co-exposure induced significantly greater neutrophils and protein levels in broncho-alveolar lavage fluid as well as a significant increase in mRNA expression of oxidative stress and inflammation related genes. Similarly, a significant increase in hydrogen peroxide production was observed after co-exposure. After single and four exposures, co-exposure revealed a greater number of differentially expressed genes (2251 and 4072, respectively). Of these genes, 1188 (single exposure) and 2061 (four exposures) were uniquely differentially expressed, with 35 mitochondrial ETC mRNA transcripts significantly impacted after four exposures. Both O3 and co-exposure treatment significantly reduced ETC maximal activity for complexes I (− 39.3% and − 36.2%, respectively) and IV (− 55.1% and − 57.1%, respectively). Only co-exposure reduced ATP Synthase activity (− 35.7%) and total ATP content (30%). Further, the ability for ATP Synthase to function is limited by reduced electron flow (− 25%) and translation of subunits, such as ATP5F1, following co-exposure. Conclusions CB and O3 co-exposure cause unique transcriptomic changes in the lungs that are characterized by functional deficits to mitochondrial bioenergetics. Alterations to ATP Synthase function and mitochondrial electron flow underly a pathological adaptation to lung injury induced by co-exposure.

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Section: Introductionmentioning

confidence: 99%

Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction

et al. 2021

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“…8). This exposure paradigm has previously demonstrated fetal growth restriction and impaired fetal coronary health www.nature.com/scientificreports/ after gestational exposure 22,24,36,38,39 . For this study we elected to leave dams and litters untouched for one week to prevent maternal rejection of the fetus.…”

Section: Methodsmentioning

confidence: 99%

Development of coronary dysfunction in adult progeny after maternal engineered nanomaterial inhalation during gestation

Fournier

Lam

Goedken

et al. 2021

Sci Rep

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Maternal exposure to environmental contaminants during pregnancy can profoundly influence the risk of developing cardiovascular disease in adult offspring. Our previous studies have demonstrated impaired cardiovascular health, microvascular reactivity, and cardiac function in fetal and young adult progeny after maternal inhalation of nano-sized titanium dioxide (nano-TiO2) aerosols during gestation. The present study was designed to evaluate the development of cardiovascular and metabolic diseases later in adulthood. Pregnant Sprague–Dawley rats were exposed to nano-TiO2 aerosols (~ 10 mg/m3, 134 nm median diameter) for 4 h per day, 5 days per week, beginning on gestational day (GD) 4 and ending on GD 19. Progeny were delivered in-house. Body weight was recorded weekly after birth. After 47 weeks, the body weight of exposed progeny was 9.4% greater compared with controls. Heart weight, mean arterial pressure, and plasma biomarkers of inflammation, dyslipidemia, and glycemic control were recorded at 3, 9 and 12 months of age, with no significant adaptations. While no clinical risk factors (i.e., hypertension, dyslipidemia, or systemic inflammation) emerged pertaining to the development of cardiovascular disease, we identified impaired endothelium-dependent and -independent arteriolar dysfunction and cardiac morphological alterations consistent with myocardial inflammation, degeneration, and necrosis in exposed progeny at 12 months. In conclusion, maternal inhalation of nano-TiO2 aerosols during gestation may promote the development of coronary disease in adult offspring.

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“…Inhalational exposures to PM2.5 and PM0.1 affect virtually all aspects of cellular functions systemically and in multiple different organs. Human and experimental animal studies showed that PM2.5 and PM0.1 elicited immune, inflammatory, oxidative, and endoplasmic reticulum stress and affected carcinogenic [45], metabolic, and epigenetic pathways [44].…”

Section: Particulate Mattermentioning

confidence: 99%

“Air That Once Was Breath” Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

Bowman,

Schmidt,

Sanghar

et al. 2024

Int Arch Allergy Immunol

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Background: Wildfires are a global concern due to their wide-ranging environmental, economic, and public health impacts. Climate change contributes to an increase in the frequency and intensity of wildfires making smoke exposure a more significant and recurring health concern for individuals with airway diseases. Some of the most prominent effects of wildfire smoke exposure are asthma exacerbations and allergic airway sensitization. Likely due to the delayed recognition of its health impacts in comparison with cigarette smoke and industrial or traffic-related air pollution, research on the composition, the mechanisms of toxicity, and the cellular/molecular pathways involved is poor or non-existent. Summary: This review discusses potential underlying pathological mechanisms of wildfire-smoke-related allergic airway disease and asthma. We focused on major gaps in understanding the role of wildfire smoke composition in the development of airway disease and the known and potential mechanisms involving cellular and molecular players of oxidative injury at the epithelial barrier in airway inflammation. We examine how PM2.5, VOCs, O3, endotoxin, microbes, and toxic gases may affect oxidative stress and inflammation in the respiratory mucosal barrier. We discuss the role of AhR in mediating smoke’s effects in alarmin release and IL-17A production and how glucocorticoid responsiveness may be impaired by IL-17A-induced signaling and epigenetic changes leading to steroid-resistant severe airway inflammation. Key Message: Effective mitigation of wildfire-smoke-related respiratory health effects would require comprehensive research efforts aimed at a better understanding of the immune regulatory effects of wildfire smoke in respiratory health and disease.

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Cardiovascular adaptations to particle inhalation exposure: molecular mechanisms of the toxicology

Cited by 22 publications

References 180 publications

Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction

Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction

Development of coronary dysfunction in adult progeny after maternal engineered nanomaterial inhalation during gestation

“Air That Once Was Breath” Part 1: Wildfire-Smoke-Induced Mechanisms of Airway Inflammation – “Climate Change, Allergy and Immunology” Special IAAI Article Collection: Collegium Internationale Allergologicum Update 2023

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