Abstract 15705: Chronic Inhaled Acrolein Depresses Circulating Endothelial Progenitor Cells and Promotes Atherosclerosis

Abstract

We have previously shown that acute exposure to air pollutants including particulate matter or the volatile acrolein leads to reversible suppression of circulating angiogenic cells in humans and mice. Exposure to tobacco smoke, which contains both particles and aldehydes such as acrolein, also suppresses EPC number and function in association with an increase in cardiovascular disease risk. To assess whether acrolein alone worsened vascular pathogenesis, we exposed mice to acrolein (1 ppm * 6h/day) in a murine model of hind limb ischemia. Mice were exposed to acrolein for 4 days prior to permanent right femoral artery and vein ligation and bisection (distal to inguinal ligament) with continued exposure to filtered air (control) or acrolein for another 2 weeks. Blood flow recovery in the ischemic hind limb was measured via Laser Doppler Perfusion Imaging (LDPI) and normalized as a percentage of flow in the non-ischemic limb. Although acute exposure to acrolein reduced the number of circulating angiogenic cells it had only a modest effect blood flow recovery after 7 days (% Recovery: air, 86.2±21.4; acrolein, 68.3±21.6, n=8,8, p=0.12). Hence to determine whether chronic acrolein exposure worsened chronic vascular injury, we exposed C57BL/6J mice to 1 ppm acrolein for 12 weeks. This long-term exposure significantly depressed (by 51%) circulating levels of Flk-1+/Sca-1+ cells (as % of lymphocytic counts: air 0.15±0.09; acrolein 0.07±0.05; p<0.02). To tested if cell changes were associated with changes in atherogenesis, apoE-null mice on normal chow or high-fat diet were exposed to chronic acrolein (1 ppm; 12 week). Acrolein accelerated aortic atherosclerosis by 1.6-fold (p<0.001) but it did not affect coincident dyslipidemia (total cholesterol: air, 1224±189; acrolein, 1076±195 mg/dL) compared with air-exposed, HFD-fed mice. These results suggest that that chronic low level acrolein exposure suppresses circulating angiogenic cells and accelerates atherogenesis; hence the atherogenic effect of exposure to traffic pollutants, indoor smoke or cigarette smoke may be in part attributable to acrolein. These findings could inform exposure risk assessments and the development of new policies for regulating pollutant exposure and tobacco product use.