title: Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries.
abstract: BACKGROUND
  Atherosclerosis affects aorta, coronary, carotid, and iliac arteries most frequently than any other body vessel. There may be common molecular pathways sustaining this process. Plaque presence and diffusion is revealed by circulating factors that can mediate systemic reaction leading to plaque rupture and thrombosis.
  
  
  RESULTS
  We used DNA microarrays and meta-analysis to study how the presence of calcified plaque modifies human coronary and carotid gene expression. We identified a series of potential human atherogenic genes that are integrated in functional networks involved in atherosclerosis. Caveolae and JAK/STAT pathways, and S100A9/S100A8 interacting proteins are certainly involved in the development of vascular disease. We found that the system of caveolae is directly connected with genes that respond to hormone receptors, and indirectly with the apoptosis pathway. Cytokines, chemokines and growth factors released in the blood flux were investigated in parallel. High levels of RANTES, IL-1ra, MIP-1 alpha, MIP-1 beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-17, PDGF-BB, VEGF and IFN-gamma were found in plasma of atherosclerotic patients and might also be integrated in the molecular networks underlying atherosclerotic modifications of these vessels.
  
  
  CONCLUSIONS
  The pattern of cytokine and S100A9/S100A8 up-regulation characterizes atherosclerosis as a proinflammatory disorder. Activation of the JAK/STAT pathway is confirmed by the up-regulation of IL-6, STAT1, ISGF3G and IL10RA genes in coronary and carotid plaques. The functional network constructed in our research is an evidence of the central role of STAT protein and the caveolae system to contribute to preserve the plaque. Moreover, Cav-1 is involved in SMC differentiation and dyslipidemia confirming the importance of lipid homeostasis in the atherosclerotic phenotype.
authors.affiliation: CRIBI Biotechnology Centre, University of Padova, Padova, Italy. stefanoc@cribi.unipd.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Cagnin
authors.forename: Michele
authors.initials: M
authors.lastname: Biscuola
authors.forename: Cristina
authors.initials: C
authors.lastname: Patuzzo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasquali
authors.forename: Paolo
authors.initials: P
authors.lastname: Laveder
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Faggian
authors.forename: Mauro
authors.initials: M
authors.lastname: Iafrancesco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mazzucco
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Lanfranchi
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D040501:Calgranulin A / Q000378:metabolism; D040502:Calgranulin B / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D050791:STAT Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D040501:Calgranulin A; D040502:Calgranulin B; D016207:Cytokines; D050791:STAT Transcription Factors