Prabhakar, S; Katwa, L; Moukdar, F; Cascio, W; Lust, R
Rationale: Epidemiology studies indicate a correlation between poor air quality and the incidence of acute cardiac events. Our lab has demonstrated previously that a single intratracheal instillation of ultrafine ambient particulate matter (PM) increases infarct size in mice or rats undergoing ischemia/reperfusion injury 24 hours later. While PMs appear to correlate with increased probability of a cardiac event, and increased injury associated with the event, very little is known about the impact of PM exposure after an event on the pattern of injury repair.
Methods: Myocardial infarction (MI) was induced in 12 male Lewis rats by permanently ligating the left anterior descending coronary artery. 4 days, 11 days and 18 days after the ligation, animals were subjected to either Diesel PM (100 µg, i.t., n = 6), or an equivalent volume of vehicle (saline, 100 µL, i.t.). Echocardiograms were performed at 7, 14 and 21 days after ligation to confirm presence of infarction. At 21 days the animals were euthanized, the hearts were excised, and the tissue was quickly frozen in Liquid N2 for subsequent analysis. qRTPCR analysis was performed to determine patterns of gene expression commonly associated with healing infarction (Type I and Type III Collagen, NFkB, MMP 1 and MMP 2).
Results: Echocardiography revealed significantly greater LV chamber dilation (LVEDD, 8.2 ± 0.4 vs. 7.1 ± 0.3 mm, p< 0.05) and decreased contractile function (Fractional Shortening, 24 ± 3 vs. 34 ± 3%, p < 0.05) in the PM group. Relative to the saline exposed MI animals, Diesel PM substantially decreased cardiac gene expression for Type I Collagen (745%, p = 0.014), Type III collagen (648%, p = 0.001), NFkB (494%, p = 0.007), MMP1 (506%, p = 0.001) and MMP2 (656%, p = 0.036) in the infarcted left ventricle.
Conclusions: These data suggest that exposure to diesel PM in the early post-infarction period adversely impacts gene expression required for cardiac remodeling, causing impaired functional recovery and increased LV chamber dilation.
