title: Acrolein impairs the cholesterol transport functions of high density lipoproteins.
abstract: High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.
authors: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors: Alexandra C
authors: AC
authors: Chadwick
authors: Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors: Rebecca L
authors: RL
authors: Holme
authors: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors: Yiliang
authors: Y
authors: Chen
authors: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors: Michael J
authors: MJ
authors: Thomas
authors: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors: Mary G
authors: MG
authors: Sorci-Thomas
authors: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors: Roy L
authors: RL
authors: Silverstein
authors: Department of Surgery, Children's Research Institute, Milwaukee, Wisconsin, United States of America.
authors: Kirkwood A
authors: KA
authors: Pritchard
authors: Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.
authors: Daisy
authors: D
authors: Sahoo
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008075:Lipoproteins, HDL; D000171:Acrolein; D002784:Cholesterol