Chronic vascular inflammation in patients with type 2 diabetes: endothelial biopsy and RT-PCR analysis.
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.


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 chi(2) 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.
Feng
Lei
L
Department of Radiology, New York Presbyterian Hospital, 177 Fort Washington Ave., MHB 8SK, New York, NY 10032, USA. lf66@columbia.edu
Matsumoto
Carolyn
C
Schwartz
Allan
A
Schmidt
Ann Marie
AM
Stern
David M
DM
Pile-Spellman
John
J
D000368:Aged; D001011:Aorta / Q000166:cytology; D001706:Biopsy / Q000379:methods*; D006328:Cardiac Catheterization; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000235:genetics / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014657:Vasculitis / Q000235:genetics / Q000473:pathology*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic