Diesel exposure has been associated with significant exacerbations in heart disease but the underlying mechanisms by which these exacerbations are mediated and the possible effects of in utero and early life exposure are poorly understood. We have found that mice exposed to diesel exhaust in utero and/or early in life develop increased left ventricular hypertrophy and a predisposition to heart failure as adults. Specificall, we have found that male mice exposed to diesel exhaust in utero and/or early in life develop left ventricular hypertrophy compared to those exposed to filtered air, while female mice exposed in utero and postnatally develop decreased ejection fraction. When the male mice undergo aortic banding, they progress more rapidly to heart failure than the filtered air controls. We hypothesize that in utero exposure to diesel exhaust creates epigenetic modifications in the hearts of exposed animals that predispose to myocardial hypertrophy and/or heart failure as adults, in possibly a gender specific fashion. Accordingly, we propose to examine genome wide epigenetic modifications in neonatal and adult mouse hearts after in utero exposure to diesel exhaust. We will also examine how these modifications vary by gender and alter global RNA expression patterns immediately after exposure and after transverse aortic constriction, a potent inducer of cardiac hypertrophy. We predict that diesel exhaust will induce epigenetic changes that alter expression of genes that confer susceptibility to hypertrophy and heart failure.
Exposure to air pollution has been linked to cardiovascular disease but the mechanisms by which it causes heart failure are unknown. Understanding how air pollution causes heart failure and how it increases susceptibility to individuals exposed prenatally or early in life will have important implications for preventing air pollution related cardiovascular illness in human populations.
| Liu, Yonggang; Weldy, Chad S; Chin, Michael T (2016) Neonatal Diesel Exhaust Particulate Exposure Does Not Predispose Mice to Adult Cardiac Hypertrophy or Heart Failure. Int J Environ Res Public Health 13: |
| Chin, Michael T (2015) Basic mechanisms for adverse cardiovascular events associated with air pollution. Heart 101:253-6 |
| Liu, Yonggang; Goodson, Jamie M; Zhang, Bo et al. (2015) Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms. Front Physiol 6:162 |
