Temporal evolution of gene expression in rat carotid artery following balloon angioplasty.
The success of vascular intervention including angioplasty, stenting, and arterial bypass remains limited by negative remodeling resulted in lumen restenosis. This study was to characterize the global transcription profile reflecting concurrent events along arterial remodeling and neointima formation in a rat carotid artery balloon-injury model. Expression profiling of injured and control common carotid arteries on days 4, 7, 14 post-injury that mark the major pathohistological progression stages of neointimal formation were recorded on high-density oligonucleotide arrays. A subset of genes from microarray-based data was further studied using quantitative real time RT-PCR and in situ hybridization with sequential arterial samples from days 1 to 28 post-injury. The gene-encoded proteins were validated with Western blot. Besides temporal induction of a large cluster of genes over-represented by cell proliferation and macromolecule metabolism gene ontology categories, a fast-evolving inflammation could be demonstrated by the induction of Tgfb and other anti-inflammatory genes (e.g., C1qtnf3 (C1q and tumor necrosis factor related protein 3 (predicted))) and a shift from type 1 to 2 helper T cell response. The most significant signature of the induced neointimal profile is enrichment of genes functionally related to angiogenesis and extracellular matrix (ECM) remodeling (e.g., Spp1 (secreted phosphoprotein 1), CD44 (CD44 antigen), and Cxcl12 (chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)). Some of the genes represent stress-responsive mesenchymal stromal cell cytokines. This study highlighted mesenchymal stromal cell cytokines-driven inflammatory extracellular matrix remodeling, as target processes for potential clinical therapeutic intervention.
Li
Jian-Ming
JM
Department of Surgery, Division of Vascular Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA. jianming.li@umassmed.edu
Zhang
Xueqing
X
Nelson
Peter R
PR
Odgren
Paul R
PR
Nelson
Janice D
JD
Vasiliu
Calin
C
Park
Jane
J
Morris
Marvin
M
Lian
Jane
J
Cutler
Bruce S
BS
Newburger
Peter E
PE
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D002339:Carotid Arteries / Q000473:pathology / Q000502:physiology / Q000601:surgery; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006965:Hyperplasia; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D036341:Intercellular Signaling Peptides and Proteins