Microarray and proteome array in an atherosclerosis mouse model for identification of biomarkers in whole blood

Int J Med Sci. 2019 Jun 2;16(6):882-892. doi: 10.7150/ijms.30082. eCollection 2019.

Abstract

Cardiovascular disease (CVD) is highly fatal, and 80 percent of the mortality is attributed to heart attack and stroke. Atherosclerosis is a disease that increases a patient's risk to CVD and is characterized by atheroma formed by immune cells, lipids, and smooth muscle cells. When an atherosclerotic lesion grows and blocks blood vessels or when an atheroma ruptures and blocks blood vessels by embolism, sudden angina, or stroke can occur. It is therefore important to diagnose atherosclerosis early and prevent its progression to more severe disease. Although myeloperoxidase, plasma fibrinogen, cardiac troponin-I, and C-reactive protein have been considered as diagnostic markers for multiple cardiac risks, specific biomarkers for atherosclerosis have not been clearly determined yet. Particularly, reliable biomarkers for the diagnosis of atherosclerosis using whole blood are not yet available. In this study, we screened potential biomarker genes and proteins from whole blood of apolipoprotein E knockout (ApoE-/- ) mice maintained on a Western diet, by comparing them to ApoE+/+ mice. We used whole blood for microarray and proteome array. Candidate genes and proteins identified from each method were confirmed with quantitative real-time PCR and ELISA. Based on our data, we speculate that Lilrb4a, n-R5s136, and IL-5 are potential targets that can be developed into novel biomarkers of atherosclerosis. Our study contributes to the diagnosis of atherosclerosis using whole blood in clinical settings.

Keywords: ApoE knockout; Atherosclerosis; biomarker; microarray; proteome array.

MeSH terms

  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / diagnosis*
  • Atherosclerosis / genetics
  • Biomarkers / blood
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Profiling
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Oligonucleotide Array Sequence Analysis
  • Protein Array Analysis
  • Proteome / analysis*
  • Proteomics

Substances

  • Biomarkers
  • Proteome