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.