Abstract 599: Exposure to Biodiesel Exhaust Triggers Atherosclerotic Plaque Destabilisation through Increased Apoptosis of Vascular Smooth Muscle Cells in the Arterial Vessel Wall

Introduction: Long-term exposure to air pollutants increases cardiovascular morbidity and mortality. Particulate matter (PM) derived from diesel exhaust has been documented to be pro-atherogenic in animal studies. Biodiesels are widely introduced as new fuels with improved emission characteristics. However, biodiesel contains relatively more polycyclic aromatic carbohydrates (PAH) compared to diesel. Therefore, we hypothesise that exposure to biodiesel as compared to diesel exhaust results in increased atherosclerosis. Methods and Results: In a carotid cuff atherosclerosis model, the effects of exposure to exhaust PM of biodiesel vs. diesel PM vs. saline (control) on atherosclerosis were evaluated. Both common carotid arteries in LDLR -/- mice were cuffed at week 2 in the course of an 8-week high-fat diet regimen. All mice were intratracheally instilled with saline, PM biodiesel or biodiesel once-weekly for 5 times. Immunohistochemistry and primary human vascular smooth muscle cells (hVSMC) were used for evaluation. Results: Exposure to both biodiesel and diesel didn’t exacerbate atherosclerosis development, however, biodiesel affected plaque composition towards a more vulnerable phenotype as compared to diesel with decreased total collagen content and hVSMC (respectively -100%, p=0.09 and -339%, p<0.01 and tend to increase necrotic core volumes (37.5% vs 28.9 % p=0.2). Exposure to biodiesel PM triggered loss of hVSMC in tunica-media, strongly correlating with apoptosis in the vessel wall (Pearson r=0.7, p<0.01). These findings were supported by dose-dependent apoptosis of hVSMCs upon 2-hour PAH treatment. Conclusions: This study demonstrates that exposure to biodiesel exhaust PM dramatically modulates atherosclerotic plaque composition, resulting in an unstable plaque phenotype through enhanced pro-apoptotic mechanisms.