Acrolein Inhalation Prevents Vascular Endothelial Growth Factor-Induced Mobilization of Flk-1(+)/Sca-1(+) Cells in Mice

作者：Wheat Laura A; Haberzettl Petra; Hellmann Jason; Baba Shahid P; Bertke Matthew; Lee Jongmin; McCracken James; O'Toole Timothy E; Bhatnagar Aruni; Conklin Daniel J^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2011, 31(7): 1598-U288.

DOI：10.1161/ATVBAHA.111.227124

• VEGF
• acrolein
• aldehydes
• endothelial dysfunction
• environmental cardiology

Objective-Acrolein is a toxic chemical present in tobacco, wood, and coal smoke, as well as automobile exhaust. Because exposure to these pollutants is associated with an increase in cardiovascular disease risk, we studied the effects of acrolein on Flk-1(+)/Sca-1(+) cells that are involved in vascular repair.
Methods and Results-In adult male C57BL/6 mice, inhalation of acrolein (1 part per million [ppm], 6 hours/day for 4 days or 5 ppm for 2 or 6 hours) led to the formation of protein-acrolein adducts in the bone marrow and diminished levels of plasma nitric oxide metabolites and circulating Flk-1(+)/Sca-1(+) but not Sca-1(+)-only cells. Acrolein exposure increased the number of apoptotic Flk-1(+)/Sca-1(+) cells in circulation and increased bone marrow-derived cells with endothelial characteristics (DiI-ac-low-density lipoprotein [DiI-acLDL]/UE-lectin and Flk-1(+)/Sca-1(+)) in culture. Deficits in the circulating levels of Flk-1(+)/Sca-1(+) cells were reversed after 7 days of recovery in acrolein-free air. Exposure to acrolein blocked vascular endothelial growth factor (VEGF)/AMD3100-stimulated mobilization of Flk-1(+)/Sca-1(+) but not Sca-1(+)-only cells and prevented VEGF-induced phosphorylation of Akt and endothelial nitric oxide synthase in the aorta.
Conclusion-Inhalation of acrolein increases apoptosis and suppresses the circulating levels of Flk-1(+)/Sca-1(+) cells while increasing these cells in the bone marrow and preventing their mobilization by VEGF. Exposure to acrolein-rich pollutants could impair vascular repair capacity. (Arterioscler Thromb Vasc Biol. 2011; 31:1598-1606.)

• 出版日期2011-7