Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women

BACKGROUND: Particulate matter (PM) exposure leads to premature death, mainly due to respiratory and cardiovascular diseases. OBJECTIVES: Identification of transcriptomic biomarkers of air pollution exposure and effect in a healthy adult population. METHODS: Microarray analyses were performed in 98 healthy volunteers (48 men, 50 women). The expression of eight sex-specific candidate biomarker genes (significantly associated with PM(10) in the discovery cohort and with a reported link to air pollution-related disease) was measured with qPCR in an independent validation cohort (75 men, 94 women). Pathway analysis was performed using Gene Set Enrichment Analysis. Average daily PM(2.5) and PM(10) exposures over 2-years were estimated for each participant’s residential address using spatiotemporal interpolation in combination with a dispersion model. RESULTS: Average long-term PM(10) was 25.9 (± 5.4) and 23.7 (± 2.3) μg/m(3) in the discovery and validation cohorts, respectively. In discovery analysis, associations between PM(10) and the expression of individual genes differed by sex. In the validation cohort, long-term PM(10) was associated with the expression of DNAJB5 and EAPP in men and ARHGAP4 (p = 0.053) in women. AKAP6 and LIMK1 were significantly associated with PM(10) in women, although associations differed in direction between the discovery and validation cohorts. Expression of the eight candidate genes in the discovery cohort differentiated between validation cohort participants with high versus low PM(10) exposure (area under the receiver operating curve = 0.92; 95% CI: 0.85, 1.00; p = 0.0002 in men, 0.86; 95% CI: 0.76, 0.96; p = 0.004 in women). CONCLUSIONS: Expression of the sex-specific candidate genes identified in the discovery population predicted PM(10) exposure in an independent cohort of adults from the same area. Confirmation in other populations may further support this as a new approach for exposure assessment, and may contribute to the discovery of molecular mechanisms for PM-induced health effects. CITATION: Vrijens K, Winckelmans E, Tsamou M, Baeyens W, De Boever P, Jennen D, de Kok TM, Den Hond E, Lefebvre W, Plusquin M, Reynders H, Schoeters G, Van Larebeke N, Vanpoucke C, Kleinjans J, Nawrot TS. 2017. Sex-specific associations between particulate matter exposure and gene expression in independent discovery and validation cohorts of middle-aged men and women. Environ Health Perspect 125:660–669; http://dx.doi.org/10.1289/EHP37

Usefulness of Thromboendarterectomy in Association with Coronary Artery Bypass Grafting

Thromboendarterectomy is sometimes performed in association with coronary artery bypass graft surgery (CABG). Right coronary arteries and severely narrowed coronary arteries mainly undergo thromboendarterectomy, but perioperative acute myocardial infarctions (AMI) are possible complications. One hundred seventy-six consecutive patients with rest and stress thallium-201 scintigraphy and angiography were studied before and after surgery. To compare patients with and without thromboendarterectomy, 48 patients who had undergone thromboendarterectomy and whose characteristics matched closely those of patients who had not were selected. Twenty patients had previous AMI before CABG in each group. Analysis accounted for the severity of vessel lesion (complete or incomplete) and for the patency of the graft and of the native coronary artery. In these 96 patients, graft patency was lower than in the overall group and similar among patients with and without thromboendarterectomy among the 56 patients without previous AMI. In patients with previous AMI and thromboendarterectomy, however, reperfusion was achieved more often through the native vessel than through the graft. New AMI or residual ischemia occurred in 32% of the areas undergoing thromboendarterectomy and in only 5% of the standard grafts (p less than 0.001). Best results were obtained in patients with incomplete occlusion after AMI. Patients without previous AMI had worse results. Thus, thromboendarterectomy can yield 64 to 75% good results in selected subgroups when CABG is otherwise impossible, but should be avoided in mildly or moderately stenotic arteries perfusing noninfarcted myocardium