Type 1 Diabetes Increases the Expression of Proinflammatory Cytokines and Adhesion Molecules in the Artery Wall of Candidate Patients for Kidney Transplantation
Open Access
- 16 January 2012
- journal article
- Published by American Diabetes Association in Diabetes Care
- Vol. 35 (2), 427-433
- https://doi.org/10.2337/dc11-1665
Abstract
OBJECTIVE: Diabetes may accelerate atheromatosis in uremic patients. Our aim was to assess the influence of type 1 diabetes on the atheromatosis-related inflammation in patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: We analyzed the expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery walls of type 1 diabetic patients with CKD (n = 22) and compared it with nondiabetic uremic patients (n = 92) at the time of kidney transplantation. We evaluated the expression of interleukin (IL)-6, monocyte chemotractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1, and the activation of nuclear factor-ÎșÎČ p65 (NFkB-p65). Common carotid intima-media thickness (c-IMT) was determined by conventional echography. RESULTS: IL-6, MCP-1, and VCAM-1 proteins were elevated in type 1 diabetic patients compared with nondiabetic subjects (P < 0.05). The nuclear localization of NFkB-p65 was higher in type 1 diabetic patients (P < 0.01) and correlated with the levels of MCP-1 in this group (r = 0.726, P < 0.001). Arterial fibrosis correlated with IL-6 and MCP-1 levels (r = 0.411, P < 0.001 and r = 0.378, P = 0.001). A significant correlation was observed between VCAM-1 levels and both the degree of arterial narrowing and c-IMT. CONCLUSIONS: Type 1 diabetes produces a proinflammatory state in the arteries of end-stage CKD patients, with increased levels of IL-6, MCP-1, and VCAM-1, as well as a greater degree of p65 activation, which are associated with more severe vascular lesions and higher c-IMT. Although causality is not demonstrated, these findings support the major role of inflammation in type 1 diabetic patients with CKD.Keywords
This publication has 31 references indexed in Scilit:
- Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathyNature Reviews Nephrology, 2011
- Interleukin 6 Mediates Myocardial Fibrosis, Concentric Hypertrophy, and Diastolic Dysfunction in RatsHypertension, 2010
- Coronary Calcification in Patients with Chronic Kidney Disease and Coronary Artery DiseaseClinical Journal of the American Society of Nephrology, 2009
- The role of the chemokines MCP-1, GRO-α, IL-8 and their receptors in the adhesion of monocytic cells to human atherosclerotic plaquesCytokine, 2008
- Evidence of Increased Inflammation and Microcirculatory Abnormalities in Patients With Type 1 Diabetes and Their Role in Microvascular ComplicationsDiabetes, 2007
- Carotid Atheromatosis in Nondiabetic Renal Transplant Recipients: The Role of Prediabetic Glucose Homeostasis AlterationsTransplantation, 2007
- A simple technique of image analysis for specific nuclear immunolocalization of proteinsJournal of Microscopy, 2007
- Intermittent high glucose enhances ICAMâ1, VCAMâ1, Eâselectin and interleukinâ6 expression in human umbilical endothelial cells in culture: the role of poly(ADPâribose) polymeraseJournal of Thrombosis and Haemostasis, 2004
- Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6Published by Oxford University Press (OUP) ,2000
- Clinical Subtypes of Alzheimerâs DiseaseDementia and Geriatric Cognitive Disorders, 1998