Transcriptomic and proteomic of peripheral blood as approaches to biomarkers cardiovascular discovers

Author(s)

Vivian Nogueira Silbiger

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2010-05-13

Examining board members

Mario Hiroyuki Hirata; Angel Carracedo Alvarez; Adriana Augusto de Rezende; Marcelo Ferraz Sampaio; Mari Cleide Sogayar

• Advisor: Mario Hiroyuki Hirata

Abstract

BACKGROUND: The main clinical manifestation of atherosclerosis is the acute myocardial infarction (AMI), which is a medical emergency that requires prompt diagnosis and efficient therapy. The transcriptomic and proteomic approaches are both powerful tools for the study of AMI and may be instrumental to identify news biomarkers involved in the inflammatory and apoptotic process of cardiovascular diseases. OBJECTIVE: The aim of this study is to determine the gene expression of RNAm and protein in blood cells following an AMI to identify new biomarkers. PATIENTS AND METHODS: For this study eighty four patients with acute coronary syndrome (ACS) and forty seven control individuals were selected among patients of the Instituto Dante Pazzanese, São Paulo state, Brazil. A global gene expression profile by GeneChip® Exon 1.0 ST Array (Affymetrix) and proteomic plasma profile by ProteinChip® Biomarker System and SELDI-TOF/MS were evaluated for ten patients from the ACS group and six from the control group. These patients were followed up for the first 48 h following the AMI. The genes differently expressed by microarray analysis were submitted to technical (same casuistic) and biologic (new casuistic) validation by PCR real time. RESULTS: 599 genes were differentially expressed at the first 48 h after AMI. Thirty-three genes were selected and submitted to the technical validation, and 20 were subjected to biological validation by real time PCR afterwards. The validated ones were: ALOX15, Areg, BCL2A1, BCL2L1, CA1, COX7B, ECDHC3, KCNE1, IL18R1, IRS2, MYL4, MMP9 and TREML4. At proteomic analysis, 479 peaks of plasma proteins differentially expressed were identified. 16 peaks were considered as high potentially biomarkers. Their molecular weight was between 6386.5 Da and 17807.7 Da. CONCLUSION: Results from this study were able to identify changes in gene and protein profiles in the plasma, and suggest new markers for evaluation of acute coronary syndrome and probably with important prognostic value. (AU)

• FAPESP's process: 06/03513-5 - Transcriptomic and proteomic approaches in the study of cardiovascular biomarkers: focus on acute myocardial infarction
• Grantee: Vivian Nogueira Silbiger
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)