Date on Master's Thesis/Doctoral Dissertation
Physiology and Biophysics
Acrolein; Endothelial progenitor cells; Hindlimb ischemia; Pollution; Vasculature; Wound healing
Acrolein--Toxicology; Stem cells--Effect of pollution on
Acrolein is a common pollutant present in ambient air, automobile exhaust, and tobacco smoke. Previous studies show that exposure to acrolein increases cardiovascular disease risk. To determine whether acrolein affect cardiovascular regeneration, we investigated the cardiovascular effects of inhaled acrolein. Adult male C57BL/6 mice were exposed to room air or acrolein (O.5, 1 or 5 ppm) for and the endothelial progenitor cells (EPC) level in peripheral blood (PB) was measured by flow cytometry. To examine the proliferative capacity of EPCs, bone marrow cells (BMCs) were cultured on fibronectin-coated slides. Brief exposure to acrolein (5 ppm, 6h) or 4 day (1 ppm) exposure led to a 42% decrease in PB Flk+/Sca+ cells. BMCs isolated from mice exposed to acrolein for 1 d (S ppm) or 4d (1 ppm) formed more colonies than BMCs of airexposed mice. Combined VEGF-A (100 µg/kg, ip, 4d) and AMD3100 (5 mg/kg; ip, last day only) treatment increased PB EPCs cells in air-exposed mice but not in acrolein-exposed mice (1 ppm, 4d). These data indicate that circulating EPCs are a sensitive target of airborne pollutants and that acrolein at concentrations encountered in tobacco smoke suppresses EPC levels in the blood but it increases the proliferative capacity of EPCs in the bone marrow. My thesis is that EPCs are sensitive targets for environmental insults, such as acrolein, thus increasing the risk of developing cardiovascular disease and endothelial dysfunction. Studies here show that the effects of acrolein on EPC after exposure by inhalation (Aim 1), the environmental pollutant acrolein, prevents mobilization of EPCs by cytokine stimulation (Aim 2), evaluated perfusion recovery of hindlimb ischemia after exposure to acrolein inhalation (Aim 3). The results of these studies support the hypothesis that exposure to environmental pollutant acrolein prevents EPC mobilization.
Nissley, Laura A. Wheat 1983-, "Effects of environmental pollution on endothelial progenitor cells and vascular regeneration." (2011). Electronic Theses and Dissertations. Paper 1065.