Laboratory InvestigationEarly Changes of Gene Expression Profiles in the Rat Model of Arterial Injury
Section snippets
Study Design
As shown on the flowchart depicting the study design (Fig 1), a total of 32 rats were used in the study. The animals were euthanized with isoflurane 5, 10, or 20 hours after vascular injury, and the injured left common carotid arteries (CCAs) were harvested (n = 8 animals in each group). Arteries were rinsed with phosphate-buffered saline solution to remove blood. Uninjured left CCAs from an additional eight animals were used as controls. Total RNA was isolated from whole arteries (n = 4 per
Time-Dependent Changes in Gene Expression Profiles
A total of 2,480 genes were differentially expressed at one or more of the designated sampling times (P < .005; more than twofold change in gene expression). In the group of genes known to be associated with an inflammatory response, 74% were upregulated at one or more time intervals (Fig 2). Four temporal clusters of gene expression were revealed (Fig 3a): genes that reached maximum expression at 5 hours after injury and then decreased (cluster I), genes upregulated at 5 hours with sustained
Discussion
Restenosis and vein graft disease remains a limitation of long-term patency after vascular reconstructions. These interventions trigger vessel wall repair processes with activation of the SMCs and inflammatory responses, which lead to the formation of IH and lesions that jeopardize patency of the reconstructed vessel segment. To develop strategies to prevent IH, it is crucial to understand the molecular pathways that control SMC function in vessel wall healing. Although previous studies have
Acknowledgments
The authors thank Mariette Lengquist for excellent help with double immunostaining.
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The work was supported by grants from the Ministry of Education and Science of the Russian Federation (project P1308), RFBR (project 14-04-01833), Swedish Heart–Lung Foundation, Swedish Research Council, and Cardiovascular Program funded by the Stockholm Council and Karolinska Institutet. None of the authors have identified a conflict of interest.
An Appendix, Figures E1 and E2, and Tables E1–E3 are available online at www.jvir.org. A list of gene and protein abbreviations used is provided in the Appendix.