Fig. 3
Circulatory cGMP and DNA damage mediating the effect of diesel exhaust exposure on HCAEC activation. In mediation analysis (A), the c coefficient denotes the direct effect of diesel exhaust exposure on HCAEC activation, without controlling for circulatory cGMP and DNA damage (mediators). HCAEC activation was expressed as RQ. The c' coefficient denotes the direct effect of diesel exhaust exposure on HCAEC activation, controlling for two mediators. The proportion mediated is equal to (sum of a*b)/(sum of a*b + c'). We took a permutation-based method to assess whether the proportion mediated was statistically significant or not (B). The relationship between CCL5 expression and the vector of independent variables was permuted for 200 times. Each permutated database allowed the association analysis of cGMP or DNA damage with internal dose of diesel exhaust exposure and other covariates to calculate a and of CCL5 expression with internal dose of diesel exhaust exposure and other covariates without and with including mediators to calculate the c, b, and c'. Permutation was conducted for 200 times to generate the distribution of sum of a*b under null hypothesis of no mediation. Value of sum of a*b calculated using observed data was compared to the distribution generated by permutation and Pperm was calculated as the number of permuted databases generating sum of a*b that is greater than observed value (0.18) divided by 200