Gene expression after crush injury of human saphenous vein: Using microarrays to define the transcriptional profile1

Price, Ray M.; Tulsyan, Nirman; Dermody, James J.; Schwalb, Marvin; Soteropoulos, Patricia; Castronuovo, John J.

doi:10.1016/j.jamcollsurg.2004.04.023

« Previous Next »Journal of the American College of Surgeons
Volume 199, Issue 3 , Pages 411-418, September 2004

Gene expression after crush injury of human saphenous vein: Using microarrays to define the transcriptional profile¹

Abstract presented at the American College of Surgeons 89^th Annual Clinical Congress, Surgical Forum, Chicago, IL, October 2003.

Ray M. Price, PhD
- Department of Surgery, Morristown Memorial Hospital, Atlantic Health System, Morristown, NJ, USA
Nirman Tulsyan, MD
- Department of Surgery, Morristown Memorial Hospital, Atlantic Health System, Morristown, NJ, USA
James J. Dermody, PhD (FACMC)
- Center for Human and Molecular Genetics, UMDNJ—the University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
- Department of Microbiology and Molecular Genetics, UMDNJ—the University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
Marvin Schwalb, PhD
- Center for Human and Molecular Genetics, UMDNJ—the University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
- Department of Microbiology and Molecular Genetics, UMDNJ—the University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
Patricia Soteropoulos, PhD
- Center for Applied Genomics, Public Health Research Institute, Newark, NJ, USA
- Department of Microbiology and Molecular Genetics, UMDNJ—the University of Medicine and Dentistry of New Jersey, Newark, NJ, USA
John J. Castronuovo Jr, MD (FACS)
- Department of Surgery, Morristown Memorial Hospital, Atlantic Health System, Morristown, NJ, USA
- Correspondence address: John J Castronuovo Jr, MD, Department of Surgery, Morristown Memorial Hospital, Atlantic Health System, 100 Madison Ave, Morristown, NJ 07962-1956 USA

Received 30 December 2003; received in revised form 2 April 2004; accepted 29 April 2004.

Abstract

Background

Vein graft stenosis is believed to be the pathophysiologic response of vascular tissue to injury and is the major cause of vein graft failure. Therapeutic interventions might improve with knowledge of the physiologic pathways involved in the hyperplastic response to vascular injury. In this study, our purpose was to identify induced, early pathways that might be important in the human response to vascular injury.

Study design

Human saphenous vein from 7 patients was organ cultured or crush injured and cultured for 48 or 72 hours after harvest. Gene expression was determined for syngeneic veins at harvest and at the experimental time points and compared to determine which genes were induced or repressed. Expressed genes (the transcriptional profile) were then assigned to functional physiologic classes.

Results

At 72 hours, in both organ-cultured and crush-injured vein, the gene for the Wnt ligand protein (WNT5A) was induced. At 48 hours in the organ-cultured vein only, the gene for the Frizzled protein (FZD2), a subunit of the Wnt receptor complex, was repressed. At 72 hours in injured vein only, the gene for the product of Wnt signaling (WISP1) was induced; the gene for the Wnt-binding, soluble Frizzled-related protein (FRZB) was repressed; and the gene for Dickkopf (DKK1) protein, which binds to the low density lipoprotein receptor-related protein subunit of the Wnt receptor complex, was induced.

Conclusions

Early induction of WNT5A, coupled with the coordinated induction and repression of genes that modulate the Wnt signaling pathway, led to the early, selective induction of WISP1 and no other Wnt-inducible genes. This early, selective expression of a limited gene set might characterize the human vascular response to injury, and could enable development of therapies to treat the clinical sequelae of this response.

Abbreviations: LRP, low density lipoprotein receptor-related protein, PCR, polymerase chain reaction, SOM, self-organizing maps