Association Between Traffic Count and Cardiovascular Mortality: A Prospective Cohort Study in Taiwan.

BACKGROUND: Exposure to traffic-related pollution is positively associated with cardiovascular diseases (CVD), but little is known about how different sources of traffic pollution (eg, gasoline-powered cars, diesel-engine vehicles) contribute to CVD. Therefore, we evaluated the association between exposure to different types of engine exhaust and CVD mortality. METHODS: We recruited 12,098 participants from REVEAL-HBV cohort in Taiwan. The CVD mortality in 2000-2014 was ascertained by the Taiwan Death Certificates. Traffic pollution sources (2005-2013) were based on information provided by the Directorate General of Highway in 2005. Exposure to PM2.5 was based on a land-use regression model. We applied Cox proportional hazard models to assess the association of traffic vehicle exposure and CVD mortality. A causal mediation analysis was applied to evaluate the mediation effect of PM2.5 on the relationship between traffic and CVD mortality. RESULTS: A total of 382 CVD mortalities were identified from 2000 to 2014. We found participants exposed to higher volumes of small car and truck exhausts had an increased CVD mortality. The adjusted hazard ratio (HR) was 1.10 for small cars (95% confidence interval [CI], 0.94-1.27; P-value = 0.23) and 1.24 for truck (95% CI, 1.03-1.51; P-value = 0.03) per one unit increment of the logarithm scale. The findings were still robust with further adjustment for different types of vehicles. A causal mediation analysis revealed PM2.5 had an over 60% mediation effect on traffic-CVD association. CONCLUSIONS: Exposure to exhaust from trucks or gasoline-powered cars is positively associated with CVD mortality, and air pollution may play a role in this association.

Hyperglycemia induced down-regulation of renal P-glycoprotein expression.

The purpose of this study is to investigate the regulation of P-glycoprotein expression in the kidney under diabetic condition. Renal P-glycoprotein expression was examined in inbred mice with type 1 or type 2 diabetes by Western blotting. The underlying mechanisms of P-glycoprotein regulation were examined in Madin-Darby canine kidney type II (MDCK-II) cells by Western blotting or qRT-PCR. (3)H-digoxin uptake was measured for P-glycoprotein activity in cells under various treatments. The results showed that P-glycoprotein expression was lower in kidneys of diabetic mice than in controls. In MDCK-II cells, treatments with insulin or IL-6 did not cause any change in P-glycoprotein expression, whereas TNF-α tended to increase P-glycoprotein expression at a concentration of 1 ng/ml. On the other hand, P-glycoprotein expression was reduced under high glucose conditions (450 mg/dl), while superoxide production was increased, and the reduction in P-glycoprotein expression was abolished by N-acetylcysteine (an antioxidant) and staurosporine (a nonselective PKC inhibitor). Treatment with oxidizing agents (H(2)O(2), BSO) or PMA (a PKC activator) reduced P-glycoprotein expression. Antioxidant (N-acetylcysteine or glutathione) co-treatment abolished the H(2)O(2)-induced and BSO-induced reduction in P-glycoprotein expression, whereas it did not prevent the effect of PMA. The PMA-induced P-glycoprotein down-regulation was prevented by co-treatment of LY333531 (a PKC-ß inhibitor). (3)H-digoxin levels were higher in MDCK-II cells with high glucose, PMA or H(2)O(2) treatments. In conclusion, P-glycoprotein expression is lower in kidneys of diabetic mice and in MDCK-II cells under high glucose conditions. Hyperglycemia induced reactive oxygen species and activated PKC in MDCK-II cells, leading to the decrease in P-glycoprotein expression.

Hypoxia-mediated down-regulation of OCTN2 and PPARα expression in human placentas and in BeWo cells.

The objective of the present study was to investigate the effects of hypoxia on placental expression of OCTN2 and PPARα. OCTN2 and PPARα expression in the human placenta in the presence or absence of preeclampsia was examined by immunohistochemical (IHC) analysis, Western blotting, and quantitative polymerase chain reaction (qPCR). Effects of hypoxia on the expression of OCTN2 and PPARα in human placental explants and human choriocarcinoma BeWo cells were examined by Western blotting and qPCR analyses. IHC, Western blot, and qPCR studies showed that OCTN2 and PPARα protein and mRNA levels were lower in syncytiotrophoblasts from preeclamptic human placentas than in those from normal placentas. Hypoxic treatment caused a decrease in OCTN2 and PPARα expression in human placental explants and in BeWo cells. WY14643, a PPARα agonist, caused an increase in OCTN2 expression in BeWo cells under hypoxic conditions. In conclusion, under hypoxic conditions, placental OCTN2 is down-regulated through PPARα-mediated pathways.