Influence of diabetes on the exacerbation of an inflammatory response in cardiovascular tissue.
Coronary artery disease results from an inflammatory process in blood vessels of afflicted individuals. This process is accelerated with diabetes for reasons that are largely unknown. Recent evidence indicates that infection at sites remote from the heart leads to bacteremia and endotoxemia, thereby stimulating systemic inflammation, which represents an important risk factor for atherosclerosis. We examined the inflammatory response of the heart/aorta of diabetic db/db mice that develop type II diabetes. Subcutaneous inoculation of lipopolysaccharide was used to mimic a local infection. This stimulated an up-regulation of adhesion molecules, cytokines, and chemokines via an endotoxemia that was significantly more rapid and more pronounced in the diabetic compared with normal mice. The 13- to 30-fold induction of key proinflammatory molecules in the heart/aorta of diabetic mice even exceeded that at the site of inoculation. Given that infection, bacteremia, and endotoxemia are relatively frequent events in humans, these results identify a putative mechanism for increased cardiovascular heart disease in diabetes.
Boston University School of Dental Medicine, W-202D, 700 Albany Street, Boston, Massachusetts 02118, USA.
Huafei
H
Lu
Markos
M
Raptis
Elena
E
Black
Maria
M
Stan
Salomon
S
Amar
Dana T
DT
Graves
D000818:Animals; D001011:Aorta / Q000276:immunology; D003324:Coronary Artery Disease / Q000209:etiology / Q000276:immunology*; D003331:Coronary Vessels / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000276:immunology*; D019446:Endotoxemia / Q000150:complications / Q000276:immunology; D005260:Female; D007375:Interleukin-1 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha