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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 13.
Published online 2009 January 9. doi:  10.1186/1471-2164-10-13
PMCID: PMC2654039
Copyright © 2009 Cagnin et al; licensee BioMed Central Ltd.
Reconstruction and functional analysis of altered molecular pathways in human atherosclerotic arteries
Stefano Cagnin,#1,2 Michele Biscuola,#3 Cristina Patuzzo,3 Elisabetta Trabetti,3 Alessandra Pasquali,3 Paolo Laveder,2 Giuseppe Faggian,4 Mauro Iafrancesco,4 Alessandro Mazzucco,4 Pier Franco Pignatti,corresponding author3 and Gerolamo Lanfranchicorresponding author1,2
1CRIBI Biotechnology Centre, University of Padova, Padova, Italy
2Department of Biology, University of Padova, Padova, Italy
3Department of Mother and Child, Biology and Genetics, Section of Biology and Genetics, University of Verona, Verona, Italy
4Division of Cardiac Surgery, University of Verona Medical School, Verona, Italy
corresponding authorCorresponding author.
#Contributed equally.
Stefano Cagnin: stefanoc/at/cribi.unipd.it; Michele Biscuola: michele.biscuola/at/gmail.com; Cristina Patuzzo: cristina.patuzzo/at/medicina.univr.it; Elisabetta Trabetti: elisabetta.trabetti/at/univr.it; Alessandra Pasquali: alessandra.psq/at/gmail.com; Paolo Laveder: paolo.laveder/at/unipd.it; Giuseppe Faggian: giuseppe.faggian/at/univr.it; Mauro Iafrancesco: mauro.iaf/at/libero.it; Alessandro Mazzucco: alessandro.mazzucco/at/univr.it; Pier Franco Pignatti: pierfranco.pignatti/at/univr.it; Gerolamo Lanfranchi: gerolamo.lanfranchi/at/unipd.it
Received September 16, 2008; Accepted January 9, 2009.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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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-1alpha, MIP-1beta, 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.
Conclusion
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.
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