Differential association of hemoglobin with proinflammatory high density lipoproteins in atherogenic/hyperlipidemic mice. A novel biomarker of atherosclerosis.
Studies in both mice and humans suggest that the anti- or proinflammatory nature of high density lipoprotein (HDL) may be a more sensitive predictor of risk for coronary heart disease events. In this study, we report the identification and characterization of two proteins (m/z 14,900 and 15,600) that are most dramatically associated with HDL in mouse models of atherosclerosis. Mass spectral analyses of proinflammatory HDL identified the two peaks to be hemoglobin (Hb) alpha and beta chains, respectively, with no apparent post-translational modification. Biochemical analysis confirmed the differential association of Hb with HDL from hyperlipidemic mice. We further show that HDL-associated Hb is predominantly in the oxyHb form with distinct physical and chemical properties. Furthermore oxyHb-containing proinflammatory HDL potently consumed nitric oxide and contracted arterial vessels ex vivo. Moreover Hb also was found differentially associated with HDL from coronary heart disease patients compared with healthy controls. Our data suggest that Hb contributes to the proinflammatory nature of HDL in mouse and human models of atherosclerosis and may serve as a novel biomarker for atherosclerosis.
Watanabe
Junji
J
Atherosclerosis Research Unit, Department of Medicine/Cardiology, University of California, Los Angeles, California 90095, USA.
Chou
Katherine J
KJ
Liao
James C
JC
Miao
Yunan
Y
Meng
Hsiang-Hui
HH
Ge
Helen
H
Grijalva
Victor
V
Hama
Susan
S
Kozak
Kathy
K
Buga
Georgette
G
Whitelegge
Julian P
JP
Lee
Terry D
TD
Farias-Eisner
Robin
R
Navab
Mohamad
M
Fogelman
Alan M
AM
Reddy
Srinivasa T
ST
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D006949:Hyperlipidemias / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation; D008074:Lipoproteins / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D012306:Risk
D015415:Biomarkers; D006454:Hemoglobins; D008074:Lipoproteins; D008075:Lipoproteins, HDL