Transcriptional profile characterization for the identification of peripheral blood biomarkers in patients with cerebral aneurysms

Giovanni Sabatino, Alessio Albanese, Enrico Marchese, Luigi Rigante, Giada Novelli, Giuseppe Maria Della Pepa, Giuseppe Esposito, Giulio Maira, D. Minella, G. Novelli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)

Abstract

We tried to identify molecular markers in peripheral blood to predict high risk of aneurysm rupture. Extraction of the total population of peripheral blood mononuclear cell (PBMC) from total blood volume, total RNA extraction from PBMC and Agilent One Color Gene-expression Oligo-Microarray were performed on peripheral venous blood samples from 45 patients with ruptured, unruptured cerebral aneurysms and control group (15). Mean foreground/ background signal intensities and A (log2(R*G)/2) values were calculated for each spot. Genes with absolute fold change (FC) greater than or equal to plus or minus 1.5 and p-value less than 0.05 were considered differentially expressed in the 3 groups (Student T-test). Genes coding for MMPs were strongly underexpressed in ruptured aneurysms group, suggesting a possible role in aneurysms development more than their rupture. Genes coding for adhesine proteins of the extracellular matrix (ICAM1) and cytoskeleton (WIPF1,TUBA4A) were underexpressed in ruptured aneurysms. Genes coding proteins involved in the regulation of apoptotic processes may be important in aneurysm development and rupture, resulting into an increased rate of remodeling processes in the arterial wall. Fas coding gene, SUMO1, ZFAT, BCL2, CCR5 genes were all over-represented in unruptured aneurysms. The coexisting over-representation of pro-apoptotic genes and the underexpression of cytoskeleton and extracellular matrix genes confirms that aneurysms development and evolution are part of a degenerative process of the arterial wall not involved in aneurysms rupture. MMPs may be involved in repairing chronic damages to the arterial walls and preventing SAH. Unexpectedly, Heat Shock Proteins (HSP90AA1, HSPA1A, HSPB1), G and RAS proteins, generally activated by stress situations were under-represented in aneurysmal walls. Further PCR and Western Blotting studies are needed to confirm such findings and to identify diagnostic and prognostic markers in order to define screening protocols for intracranial aneurysms.
Lingua originaleEnglish
pagine (da-a)729-738
Numero di pagine10
RivistaJOURNAL OF BIOLOGICAL REGULATORS & HOMEOSTATIC AGENTS
Volume27
Stato di pubblicazionePubblicato - 2013

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Markers
  • Female
  • Humans
  • Intracranial Aneurysm
  • Male
  • Matrix Metalloproteinases
  • Middle Aged
  • Transcriptome

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