Temporal gene expression following prosthetic arterial grafting.
BACKGROUND
Following prosthetic arterial grafting, cytokines and growth factors released within the perianastomotic tissues stimulate smooth muscle cell proliferation and matrix production. While much in vitro work has characterized this response, little understanding exists regarding the sequential up- and down-regulation of genes following prosthetic arterial grafting. This study evaluates temporal gene expression at the distal anastomosis of prosthetic arterial grafts using microarray analysis.


METHODS
Expanded polytetrafluoroethylene (ePTFE) carotid interposition grafts (n = 12) were surgically implanted into mongrel dogs. Distal anastomotic segments were harvested at 7, 14, 30, or 60 days. Contralateral carotid artery served as control. Total RNA was isolated from the anastomotic tissue and paired controls. Samples were probed with oligonucleotide microarrays consisting of approximately 10000 human genes to analyze differential gene expression at each time point.


RESULTS
Forty-nine genes were found to be up-regulated and 37 genes were found to be down-regulated at various time points. Six genes were found to be consistently up-regulated at all time intervals, including collagen type 1 alpha-1 and alpha-2, 80K-L protein (MARCKS), and osteopontin. Six genes were found to be consistently down-regulated, including smoothelin and tropomyosin 2. RT-PCR and immunohistochemistry confirmed the microarray data.


CONCLUSIONS
This study uses microarray analysis to identify genes that were temporally up- and down-regulated after prosthetic arterial grafting. Genes with similar patterns of expression have been identified, providing insights into related cellular pathways that may result in the formation of anastomotic intimal hyperplasia.
Willis
David J
DJ
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA. willid01@popmail.med.nyu.edu
Kalish
Jeffrey A
JA
Li
Cheng
C
Deutsch
Evan R
ER
Contreras
Mauricio A
MA
LoGerfo
Frank W
FW
Quist
William C
WC
D000714:Anastomosis, Surgical; D000818:Animals; D001158:Arteries / Q000601:surgery; D019917:Blood Vessel Prosthesis Implantation; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D004285:Dogs; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors
D016207:Cytokines; D006133:Growth Substances