Impact of insulin resistance on enhanced monocyte adhesion to endothelial cells and atherosclerogenesis independent of LDL cholesterol level.
Epidemiological studies suggest that insulin resistance is an independent risk factor for cardiovascular disease. However, there is little information on the role of insulin resistance in atherosclerogenesis independent of LDL cholesterol level. The aim of this study was to investigate the impact of systemic insulin resistance on monocyte adhesion to endothelial cells and atherosclerotic lesions independent of LDL cholesterol level. KKAy mice are obese mice with spontaneous diabetes and insulin resistance, and normal levels of LDL cholesterol. In parallel with systemic insulin resistance, decreased insulin signal, and the increased expression of monocyte chemoattractant protein-1 (MCP-1) were noted in macrophages isolated from KKAy mice. These mice showed enhanced monocyte adhesion to the endothelial cells of the thoracic artery. Furthermore, these mice showed expanded atherosclerotic lesions when fed high cholesterol diet. Our data indicate that insulin resistance promotes the atherosclerogenesis independent of LDL cholesterol level. Decreased insulin signaling in macrophages associated with systemic insulin resistance could be involved, at least in part, in this pathological process.
Mita
Tomoya
T
Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Goto
Hiromasa
H
Azuma
Kosuke
K
Jin
Wen Long
WL
Nomiyama
Takashi
T
Fujitani
Yoshio
Y
Hirose
Takahisa
T
Kawamori
Ryuzo
R
Watada
Hirotaka
H
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D004032:Diet; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000473:pathology* / Q000502:physiology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D008078:Cholesterol, LDL