Increased inflammation in atherosclerotic lesions of diabetic Akita-LDLr−/− mice compared to nondiabetic LDLr−/− mice

Engelbertsen D, To F, Duner P, Kotova O, Soderberg I, Alm R, Gomez MF, Nilsson J, Bengtsson E.
Journal   Experimental Diabetes Research
Species  
Analytes Measured   IL-10 , IL-12 Total , IL-2 , IL-4 , IL-5
Matrix Tested   Plasma
Year   2012
Volume   2012
Page Numbers  
Application   Cytokines and Chemokines
Abstract
Background: Diabetes is associated with increased cardiovascular disease, but the underlying cellular and molecular mechanisms are poorly understood. One proposed mechanism is that diabetes aggravates atherosclerosis by enhancing plaque inflammation. The Akita mouse has recently been adopted as a relevant model for microvascular complications of diabetes. Here we investigate the development of atherosclerosis and inflammation in vessels of Akita mice on LDLr−/− background.

Methods and Results: Akita-LDLr−/− and LDLr−/− mice were fed high-fat diet from 6 to 24 weeks of age. Blood glucose levels were higher in both male and female Akita-LDLr−/− mice (137% and 70%, resp.). Male Akita-LDLr−/− mice had markedly increased plasma cholesterol and triglyceride levels, a three-fold increase in atherosclerosis, and enhanced accumulation of macrophages and T-cells in plaques. In contrast, female Akita-LDLr−/− mice demonstrated a modest 29% increase in plasma cholesterol and no significant increase in triglycerides, atherosclerosis, or inflammatory cells in lesions. Male Akita-LDLr−/− mice had increased levels of plasma IL-1β compared to nondiabetic mice, whereas no such difference was seen between female diabetic and nondiabetic mice.

Conclusion: Akita-LDLr−/− mice display considerable gender differences in the development of diabetic atherosclerosis. In addition, the increased atherosclerosis in male Akita-LDLr−/− mice is associated with an increase in inflammatory cells in lesions.

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CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-2 Kit
IL-2 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-2 Antibody
IL-2
Human IL-4 Antibody
IL-4
Human IL-5 Antibody
IL-5
Human IL-10 Antibody
IL-10
Mouse IL-2 Antibody
IL-2
Mouse IL-4 Antibody
IL-4
Mouse IL-5 Antibody
IL-5
Mouse IL-10 Antibody
IL-10
Rat IL-4 Antibody
IL-4
Rat IL-5 Antibody
IL-5
Rat IL-10 Antibody
IL-10
V-PLEX Cytokine Panel 1 Human Kit
GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-2 Kit
IL-2 | Human
Singleplex
V-PLEX Human IL-5 Kit
IL-5 | Human
Singleplex
V-PLEX Human IL-10 Kit
IL-10 | Human
Singleplex
V-PLEX Mouse IL-2 Kit
IL-2 | Mouse
Singleplex
V-PLEX Mouse IL-4 Kit
IL-4 | Mouse
Singleplex
V-PLEX Mouse IL-5 Kit
IL-5 | Mouse
Singleplex
V-PLEX Mouse IL-10 Kit
IL-10 | Mouse
Singleplex
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