Combined Plasma and Tissue Proteomic Study of Atherogenic Model Mouse: Approach To Elucidate Molecular Determinants in Atherosclerosis Development.
Atherogenic cardiovascular diseases are the major cause of mortality. Prevention and prediction of incidents is important; however, biomarkers that directly reflect the disease progression remain poorly investigated. To elucidate molecular determinants of atherogenesis, proteomic approaches are advantageous by using model animals for comparing changes occurring systematically (bloodstream) and locally (lesion) in accordance with the disease progression stages. We conducted differential mass spectrometric analysis between apolipoprotein E deficient (apoED) and wild-type (wt) mice using the plasma and arterial tissue of both types of mice obtained at four pathognomonic time points of the disease. A total of 100 proteins in the plasma and 390 in the arterial tissues were continuously detected throughout the four time points; 29 were identified in common. Of those, 13 proteins in the plasma and 36 in the arterial tissues showed significant difference in abundance between the apoED and wt mice at certain time points. Importantly, we found that quantitative variation patterns regarding the pathognomonic time points did not always correspond between the plasma and arterial tissues, resulting in gaining insight into atherosclerotic plaque progression. These characteristic proteins were found to be components of inflammation, thrombus formation, and vascular remodeling, suggesting drastic and integrative alteration in accordance with atherosclerosis development.
Center for Exploratory Research, Research & Development Group, Hitachi, Ltd. , 350-0395 Hatoyama, Saitama Japan.|Central Institute of Isotope Science, Hokkaido University , 060-0814 Sapporo, Japan.
Hiroko
H
Hanzawa
Center for Technology Innovation - Healthcare, Research & Development Group, Hitachi, Ltd. , 185-8601 Kokubunji, Japan.|Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University , 060-8638 Sapporo, Japan.
Takeshi
T
Sakamoto
Center for Technology Innovation - Healthcare, Research & Development Group, Hitachi, Ltd. , 185-8601 Kokubunji, Japan.
Akihito
A
Kaneko
Center for Technology Innovation - Healthcare, Research & Development Group, Hitachi, Ltd. , 185-8601 Kokubunji, Japan.|Central Institute of Isotope Science, Hokkaido University , 060-0814 Sapporo, Japan.
Naomi
N
Manri
Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University , 060-8638 Sapporo, Japan.
Yan
Y
Zhao
Department of Tracer Kinetics & Bio-analysis, Graduate School of Medicine, Hokkaido University , 060-8638 Sapporo, Japan.
Songji
S
Zhao
Department of Nuclear Medicine, Graduate School of Medicine, Hokkaido University , 060-8638 Sapporo, Japan.
Nagara
N
Tamaki
Central Institute of Isotope Science, Hokkaido University , 060-0814 Sapporo, Japan.|Department of Integrated Molecular Imaging, Graduate School of Medicine, Hokkaido University , 060-8638 Sapporo, Japan.
Yuji
Y
Kuge
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001158:Arteries / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000302:isolation & purification*; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058977:Molecular Sequence Annotation; D010446:Peptide Fragments / Q000032:analysis; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D013194:Staining and Labeling; D053719:Tandem Mass Spectrometry; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014357:Trypsin; D066253:Vascular Remodeling
D001057:Apolipoproteins E; D015415:Biomarkers; D001798:Blood Proteins; D010446:Peptide Fragments; D014357:Trypsin
apoE deficient mouse; atherosclerosis; coagulation; complement; extracellular matrix; fibrinolysis; inflammation; macrophage; proteomic study