Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. Particulate matter-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease anti-oxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2 deficient (SOD2+/-) mice which possess decreased anti-oxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2+/- mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2+/- mouse aortas, and relaxation was significantly reduced in young SOD2+/- compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2+/- mice. Data demonstrate that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of anti-oxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2+/- mice. This dataset is associated with the following publication: Carter, J., N. Madamanchi , G. Stouffer, M. Runge, W. Cascio, and H. Tong. Ultrafine Particulate Matter Exposure Impairs Vasorelaxant Response in Superoxide Dismutase 2 Deficient Murine Aortic Rings. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 81(5): 106-115, (2018).

The dataset contains data of air pollution, blood lipids, vascular injury markers, coagulation markers, and heart rate variability and repolarization markers. This dataset is associated with the following publication: Chen, H., S. Zhang, W. Shen, C. Salazar, A. Schneider, A. Rappold, D. Diazsanchez, R. Devlin, J. Samet, and H. Tong. Omega-3 Fatty Acids Attenuate Cardiovascular Effects of Short-term Exposure to Ambient Air Pollution. Particle and Fibre Toxicology. BioMed Central Ltd, London, UK, 19(12): 1, (2022).

Background: Adverse cardiovascular events have been linked with PM2.5 exposure obtained primarily from air quality monitors, which rarely co-locate with participant residences. Modeled PM2.5 predictions at finer resolution may more accurately predict residential exposure; however few studies have compared results across different exposure assessment methods. Methods: We utilized a cohort of 5679 patients who had undergone a cardiac catheterization between 2002–2009 and resided in NC. Exposure to PM2.5 for the year prior to catheterization was estimated using data from air quality monitors (AQS), Community Multiscale Air Quality (CMAQ) fused models at the census tract and 12 km spatial resolutions, and satellite-based models at 10 km and 1 km resolutions. Case status was either a coronary artery disease (CAD) index>23 or a recent myocardial infarction (MI). Logistic regression was used to model odds of having CAD or an MI with each 1-unit (μg/m3) increase in PM2.5, adjusting for sex, race, smoking status, socioeconomic status, and urban/rural status. Results: We found that the elevated odds for CAD>23 and MI were nearly equivalent for all exposure assessment methods. One difference was that data from AQS and the census tract CMAQ showed a rural/urban difference in relative risk, which was not apparent with the satellite or 12 km-CMAQ models. Conclusions: Long-term air pollution exposure was associated with coronary artery disease for both modeled and monitored data. This dataset is not publicly accessible because: EPA cannot release personally identifiable information regarding living individuals, according to the Privacy Act and the Freedom of Information Act (FOIA). This dataset contains information about human research subjects. Because there is potential to identify individual participants and disclose personal information, either alone or in combination with other datasets, individual level data are not appropriate to post for public access. Restricted access may be granted to authorized persons by contacting the party listed. It can be accessed through the following means: Clinical data are located in: C:\Users\rdevlin\OneDrive - Environmental Protection Agency (EPA)\Excel Files\Cathgen Satellite data are located in : C:\Users\rdevlin\OneDrive - Environmental Protection Agency (EPA)\Excel Files\New Ikm Satellite Data C:\Users\rdevlin\OneDrive - Environmental Protection Agency (EPA)\Excel Files\Satellite Data CMAQ data are located in C:\Users\rdevlin\OneDrive - Environmental Protection Agency (EPA)\Excel Files\CMAQ Data. Format: There are two types of datasets used in this study: clinical data taken from patient records at the Duke Medical Center; and air pollution data (PM2.5) taken from a federal reference monitor located in Raleigh, CMAQ data obtained from collaborators at Georgia Tech and NERL/ORD, and satellite data obtained from collaborators at Harvard. Metadata are in the form of Excel spreadsheets that contain columns of data that specify clinical and exposure information for each individual participating in the study. This dataset is associated with the following publication: McGuinn, L., C. Ward-Caviness, A. Schneider, Q. Di, A. Chudnovsky, J. Schwartz, P. Koutrakis, A. Russell, V. Garcia, W. Krause, E. Hauser, L. Neas, W. Cascio, D. Diaz-Sanchez, and R. Devlin. Fine Particulate Matter and Cardiovascular Disease: Comparison of Assessment Methods for Long-term Exposure. ENVIRONMENTAL RESEARCH. Academic Press Incorporated, Orlando, FL, USA, 159: 16-23, (2017).

We have examined the potential for interactive cardiovascular effects of repeated, intermittent co-exposure to concentrated ambient particulate matter (CAPs) and acrolein, and the potential role of transient receptor potential cation channel A1 (TRPA1), which we previously linked to air pollution-induced cardiac arrhythmogenesis. Chemical and source characteristics of collected particles was evaluated, as well as wind and weather patterns during exposure. Female B6129 mice and Trpa1-/- mice (n=6) were exposed to filtered air (FA), CAPs (46 µg/m3 of PM2.5 approximately 160 nm diameter), Acrolein (0.42 ppm) or CAPs+Acrolein for 3hrs/day, 2days/week, for 4 weeks. Cardiac strain data, heart function and dimensions, and transmitral blood flow were investigated with echocardiography (40 MHz) before exposures, 1 day after the first exposure, and 1 day after the final exposure. Several other biological endpoints were evaluated but the key findings from ultrasound echocardiography assessments were: elapsed time between peak strain in adjacent wall segments (i.e. myocardial strain delay), a measure of myocardial dyssynchrony, increased by ~5-fold in B6129 mice after the final exposure to CAPs+Acrolein when compared to strain delay in B6129 mice exposed to FA, CAPs, or Acrolein alone, and when compared to strain delay in Trpa1-/- mice exposed to CAPs+Acrolein. There were no changes after the first exposure in any group. This dataset is associated with the following publication: Thompson, L., L. Walsh, B. Martin, J. Mcgee, C. Wood, K. Kovalcik, P. Pancras, N. Coates, A. Ledbetter, D. Davies, W. Cascio, M. Higuchi, M. Hazari, and A. Farraj. Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice: Evidence for TRPA1 Involvement. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 167(2): 559-572, (2019).

Effects of exposure to fatty acids on the contraction and relaxation of aortic tissue (Figure 1 A-E) and the viability of the aortic tissue (Table 1). This dataset is associated with the following publication: Bass, V., S. Snow, J. Soukup, M. Schladweiler, A. Ghio, U. Kodavanti, and M. Madden. 12-Hydroxy Oleic Acid Impairs Endothelium Dependent Vasorelaxation. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 82(5): 383-386, (2020).

Aortic tissue cellular viability with different treatments. This dataset is associated with the following publication: Bass, V., S. Snow, J. Soukup, M. Schladweiler, A. Ghio, U. Kodavanti, and M. Madden. 12-Hydroxy Oleic Acid Impairs Endothelium Dependent Vasorelaxation. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH - PART A: CURRENT ISSUES. Taylor & Francis, Inc., Philadelphia, PA, USA, 82(5): 383-386, (2020).

This dataset contains data of blood miRNA, cardiovascular biomarkers (i.e. inflammation, coagulation, and blood lipids), omega-3 index levels, as well as ambient PM2.5, O3 and NO2 concentrations from the panel study "PISCES". This dataset is associated with the following publication: Chen, H., S. Zhang, B. Yu, Y. Xu, A. Rappold, D. Diaz-Sanchez, J. Samet, and H. Tong. Circulating microRNAs as putative mediators in the association between short-term exposure to ambient air pollution and cardiovascular biomarkers. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY. Elsevier Science Ltd, New York, NY, USA, 239(113604): 1, (2022).

The matricellular protein thrombospondin 2 (TSP2) regulates a variety of cell–matrix interactions. A prominent feature of TSP2-null mice is increased microvascular density, particularly in connective tissues synthesized after injury. We investigated the cellular basis for the regulation of angiogenesis by TSP2 in cultures of murine and human fibroblasts and endothelial cells. Fibroblasts isolated from murine and human dermis synthesize TSP2 mRNA and secrete significant amounts of immunoreactive TSP2, whereas endothelial cells from mouse lung and human dermis did not synthesize TSP2 mRNA or protein. Recombinant mouse TSP2 inhibited growth of human microvascular endothelial cells (HMVECs) mediated by basic fibroblast growth factor, insulin-like growth factor-1, epidermal growth factor, and vascular endothelial growth factor (VEGF). HMVECs exposed to TSP2 in the presence of these growth factors had a decreased proportion of cells in S and G2/M phases. HMVECs cultured with a combination of basic fibroblast growth factor, insulin-like growth factor-1, and epidermal growth factor displayed an increased proportion of nonviable cells in the presence of TSP2, but the addition of VEGF blocked this TSP2-mediated impairment of cell viability. TSP2-mediated inhibition of DNA synthesis by HMVECs in the presence of VEGF was not affected by the broad-spectrum caspase inhibitor zVAD-fmk. Similar findings were obtained with TSP1. Taken together, these observations indicate that either TSP2 or TSP1 can inhibit HMVEC proliferation by inhibition of cell cycle progression and induction of cell death, but the mechanisms responsible for TSP2-mediated inhibition of cell cycle progression are independent from those leading to cell death.

Background: Hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (OFR)-mediated lipid peroxidation - a process that can be measured through its byproducts, specifically malondialdehyde. The use of free radical scavengers can offer significant protection against OFR-induced liver injury. We hypothesize that a new potent OFR scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD), can inhibit OFR-mediated lipid peroxidation in hepatic ischemia/reperfusion injury. Methods: Twelve male Sprague-Dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. PEG-SOD (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. Normal saline was given to the remaining six rats to be used as a control group. The right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured. Results: A marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. Treatment with PEG-SOD prevented the rise in tissue malondialdehyde. The mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 ± 6.35 and 1.70 ± 3.65 nmol/g in the normal saline (control) and PEG-SOD groups, respectively. This difference was found to be statistically significant (P < 0.005) using Student's t-test. Conclusions: PEG-SOD can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting OFR-mediated lipid peroxidation.

The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast, treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment.