Chronic Vascular Inflammation in Patients With Type 2 Diabetes
Endothelial biopsy and RT-PCR analysis
- Lei Feng, MD, PHD1,
- Carolyn Matsumoto, BS1,
- Allan Schwartz, MD2,
- Ann Marie Schmidt, MD3,
- David M. Stern, MD3 and
- John Pile-Spellman, MD1
- 1Department of Radiology, College of Physicians and Surgeons, Columbia University, New York, New York
- 2Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York
- 3Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York
- Address correspondence and reprint requests to Lei Feng, MD, PhD, Department of Radiology, New York Presbyterian Hospital, 177 Fort Washington Ave., MHB 8SK, New York, NY 10032. E-mail: lf66{at}columbia.edu
Abstract
OBJECTIVE—Chronic vascular inflammation may play a role in the development of macrovascular complications in diabetic patients. In this study, we examine the association of endothelial expression of two inflammatory mediators, receptor for advanced glycation end product (RAGE) and monocyte chemoattractant protein-1 (MCP-1), with type 2 diabetes using novel endothelial biopsy and RT-PCR techniques.
RESEARCH DESIGN AND METHODS—Endothelial samples are obtained from the aorta of 12 patients with type 2 diabetes and 23 control subjects who underwent cardiac catheterization for chest pain syndrome or heart transplant follow-up. Endothelial cells are purified using magnetic beads with adsorbed CD146 antibody and subjected to RT-PCR analysis of RAGE and MCP-1 transcripts. The association of RAGE and MCP-1 expression with type 2 diabetes is assessed with χ2 test and confirmed with in vitro experiments on human aorta endothelial cells.
RESULTS—RT-PCR reveals gene expression patterns in patient-derived endothelial cells. Strong associations are observed between induction of RAGE mRNA and diabetes (P < 0.01) and between induction of RAGE and MCP-1 transcripts (P < 0.05). Treatment of cultured human aortic endothelial cells with S100b induces the expression of MCP-1 and RAGE transcripts.
CONCLUSIONS—Endothelial cells can be harvested during cardiac catheterization and can be characterized with respect to molecular phenotypes under the influence of both genetic and environmental factors. Induction of RAGE and MCP-1 transcripts in patients with diabetes supports a role of chronic vascular inflammation in macrovascular complications.
- AGE, advanced glycation end product
- GAPDH, glyceraldehydes-3-phosphate
- HAEC, human aortic endothelial cell
- LCA-1, leukocyte common antigen-1
- MCP-1, monocyte chemoattractant protein-1
- RAGE, receptor for AGE
- vWF, von Willebrand factor
Footnotes
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A.M.S. is a member of the Scientific Advisory Board of, has been a paid consultant for, and has received research support from TransTech Pharma.
D.M.S. is currently affiliated with the Medical College of Georgia, School of Medicine, Augusta, Georgia.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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- Accepted October 26, 2004.
- Received June 30, 2004.
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