Paul Willet

University of California, Irvine, Irvine, CA, United States

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Publications (2)3.61 Total impact

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    ABSTRACT: Exposure to ambient particulate matter (PM) significantly increases cardiovascular morbidity and mortality in the general population. We hypothesized that some components of PM can affect the gene expression patterns in the hearts of rats exposed for 3months to filtered air (FA), coarse (CP; 2.5 < dp < 10μm), fine (FP; dp ≤ 2.5μm) or ultrafine (UFP; dp ≤ 0.18μm) components of PM. The median diameters of CP, FP, and UFP were 3μm, 0.7μm and 0.07μm, respectively. Exposures (n = 8 per group) were performed using a particle concentrator system in Riverside, California, an area with high ambient levels of photochemically derived gaseous and particulate pollutants. At the end of the exposure, hearts were subjected to gene expression profiling by using Illumina RatRef-12 bead chips and levels of malonaldehyde (MDA), a biomarker of oxidative stress, were measured. Applying fold ratio >1.5 (for both up- and down-regulated genes), we found three genes in the CP and nine genes in the UFP groups with significantly changed expression, compared with FA. No significant changes in gene expression patterns were observed in the FP group. In the UFP group thioredoxin interacting protein (Txnip), a negative regulator of an antioxidant enzyme thioredoxin, and cytochrome P450 (Cyp2e1), an enzyme involved in the metabolism of foreign substances demonstrated significant up-regulation (fold ratios 1.79 and 1.57, respectively, with false discovery rate, FDR < 0.05). In the CP group there was also a trend towards increased Txnip expression (fold ratio 1.43, FDR > 0.05) and significant increase in the Cyp2e1 expression (fold ratio 1.79, FDR < 0.05). Changes in the Txnip and Cyp2e1 expression showed statistically significant positive correlation to each other (p < 0.0009) and were confirmed by real-time PCR. In addition Txnip and Cyp2e1 expression demonstrated statistically significant moderate correlation with the levels of MDA in the heart. Up-regulation of both Cyp2e1 and Txnip are observed in hearts of patients with certain cardiac diseases. Therefore, chronic exposure to CP and UFP directly affects expression of disease-relevant genes in the myocardium. KeywordsParticulate air pollution–Heart–Gene expression–Oxidative stress
    Air Quality Atmosphere & Health 01/2011; 4(1):15-25. DOI:10.1007/s11869-010-0089-0 · 1.80 Impact Factor
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    ABSTRACT: Exposure to ambient particulate matter (PM) is linked to increases in cardiovascular morbidity and mortality. The exact mechanism by which PM induces cardiovascular toxicity is not completely understood. We sought to study histopathological changes in the heart muscle in young healthy (Wistar–Kyoto, WKY) and spontaneously hypertensive (SHR) rats and old (22-month-old) Sprague–Dawley rats (SD) chronically exposed to PM. WKY rats and SHR were exposed for 3months to ultrafine particles (UFP) or filtered air (FA). SD rats were exposed for 9months to coarse (CP), fine (FP), and ultrafine particles or FA. In addition, we studied effects of PM on mean arterial blood pressure (MABP) and echocardiograms in WKY rats and SHR. Chronic exposure to PM caused histopathological changes in the hearts of all studied strains. The effects ranged from cardiac inflammation caused by 3months of exposure to UFP in WKY rats and SHR to more severe changes in SD rats exposed to PM for 9months. Changes in SD rats were inflammation, intracellular edema, and vacuolization in hearts exposed to FP and UFP and vacuolization and collagen accumulation in CP-exposed hearts. In addition, evidence of only mild inflammation was seen in the respiratory tract. We did not observe any statistically significant changes in the MABP (constantly recorded over the entire period of exposure by implanted telemetric devices) and in the echocardiograms in WKY rats and SHR exposed to UFP or FA. MABP at the end of 3months exposure comprised 153.3 ± 13.9 and 160.3 ± 14.7mmHg in the SHR-FA and SHR-UFP, respectively, and 124.4 ± 11.2 and 107.9 ± 9.2mmHg in the WKY-FA and WKY-UFP, respectively (mean ± SD). Our data indicate that chronic exposure to particulate air pollutants causes histopathological changes in healthy (WKY), diseased (SHR), and old SD rat hearts. KeywordsAir pollution–Heart–Histopathology–Echocardiogram–Inflammation
    Air Quality Atmosphere & Health 03/2010; 4(1):27-36. DOI:10.1007/s11869-010-0097-0 · 1.80 Impact Factor