World Trade Center-Cardiorespiratory and Vascular Dysfunction: Assessing the Phenotype and Metabolome of a Murine Particulate Matter Exposure Model

Abstract

Vascular changes occur early in the development of obstructive airways disease. However, the vascular remodeling and dysfunction due to World trade center-particulate Matter (Wtc-pM) exposure are not well described and are therefore the focus of this investigation. C57Bl/6 female mice oropharyngeally aspirated 200 µg of Wtc-pM 53 or phosphate-buffered saline (PBS) (controls). 24-hours (24-hrs) and 1-Month (1-M) after exposure, echocardiography, micro-positron emission tomography(µ-pet), collagen quantification, lung metabolomics, assessment of antioxidant potential and soluble-receptor for advanced glycation end products (sRAGE) in bronchoalveolar lavage(BAL) and plasma were performed. 24-hrs post-exposure, there was a significant reduction in (1) Pulmonary artery(PA) flowvelocity and pulmonary ejection time(PET) (2) Pulmonary acceleration time(PAT) and PAT/PET, while (3) Aortic ejection time(AET) and velocity time integral(VTI) were increased, and (4) Aortic acceleration time (AAT)/AET, cardiac output and stroke volume were decreased compared to controls. 1-M postexposure, there was also significant reduction of right ventricular diameter as right ventricle free wall thickness was increased and an increase in tricuspid E, A peaks and an elevated E/A. The pulmonary and cardiac standard uptake value and volume 1-M post-exposure was significantly elevated after pM-exposure. Similarly, α-smooth muscle actin(α-SMA) expression, aortic collagen deposition was elevated 1-M after PM exposure. In assessment of the metabolome, prominent subpathways included advanced glycation end products (AGEs), phosphatidylcholines, sphingolipids, saturated/ unsaturated fatty acids, eicosanoids, and phospholipids. BAL superoxide dismutase(SOD), plasma total-antioxidant capacity activity, and sRAGE (BAL and plasma) were elevated after 24-hrs. PM exposure and associated vascular disease are a global health burden. our study shows persistent Wtc-Cardiorespiratory and Vascular Dysfunction (WTC-CaRVD), inflammatory changes and attenuation of antioxidant potential after pM exposure. early detection of vascular disease is crucial to preventing cardiovascular deaths and future work will focus on further identification of bioactive therapeutic targets. The negative health effects of particulate matter (PM) exposure are a significant global burden. Epidemiologic studies demonstrate associations between PM exposure and development of lung and cardiovascular disease(CVD) 1,2. Pulmonary vascular remodeling occurs in mild non-hypoxemic chronic obstructive pulmonary

Dietary Phenotype and Advanced Glycation End-Products Predict WTC-Obstructive Airways Disease: a Longitudinal Observational Study

“…44REAP-S scores can range from 15-39, and higher quantities represent dietary quality characterized by optimal intake of fruits, vegetables, and whole grains and decreased intake of sugary foods, processed meats, and fried foods. Scores were categorized into low-dietary (15)(16)(17)(18)(19), moderatedietary (20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and high-dietary (30-39) quality, Table 3. Additionally, REAP-S questions were assessed as distinct food categories.…”

“…Speci cally, RAGE de cient WTC-PM exposed mice were protected against WTC-OAD. (25)(26)(27) Dietary and endogenous AGEs can impact signaling pathways such those in in ammatory diseases. (28) Despite evidence that diet and obesity are risks, studies have suggested obesity may have a protective effect on survival and lung function in COPD.…”

Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study

“…REAP-S scores can range from 15-39, and higher quantities represent dietary quality characterized by optimal intake of fruits, vegetables, and whole grains and decreased intake of sugary foods, processed meats, and fried foods. Scores were categorized into low-dietary [15][16][17][18][19], moderatedietary [16,[20][21][22][23][24][25][26][27][28], and high-dietary [29][30][31][32][33][34][35][36][37][38] quality, Table 3. Additionally, REAP-S questions were assessed as distinct food categories.…”

“…Our in vitro and in vivo models identified that the receptor for AGE (RAGE) is associated with lung dysfunction after WTC-particulate matter (WTC-PM) exposure. Specifically, RAGE deficient WTC-PM exposed mice were protected against WTC-OAD [ [24][25][26]. Dietary and endogenous AGEs can impact signaling pathways such as those in inflammatory diseases [27].…”

Dietary Phenotype and Advanced Glycation End-Products Predict WTC-Obstructive Airways Disease: a Longitudinal Observational Study

“…Speci cally, RAGE de cient WTC-PM exposed mice were protected against WTC-OAD. (24)(25)(26) Dietary and endogenous AGEs can impact signaling pathways such those in in ammatory diseases. (27) Despite evidence that diet and obesity are risks, studies have suggested obesity may have a protective effect on survival and lung function in COPD.…”