Interleukin 18 (IL-18) is a pro-inflammatory cytokine with pro-atherogenic properties whose level can be elevated by psychological stress. Since stress contributes to atherosclerosis we hypothesized that IL-18 is one of the mediators of the stress- dependent development of atherosclerosis. To test this hypothesis we will use the atherosclerosis prone mice null for Apolipoprotein E (ApoE-/-) and in mice null for mice Apolipoprotein E and IL-18 (ApoE-/- IL-18-/-). ApoE-/- and ApoE-/- IL-18-/- mice will be divided in two groups, one receiving stress and one will be left undisturbed. The effects of stress and of IL-18 on atherosclerosis will be evaluated by investigating: 1. the percentage of aorta containing lesions; 2. the morphometric analysis of the lesions; 3. the histochemical analysis of the lesions; 4. the level of stress-related or IL-18 induced pro-atherogenic molecules. These experiments will determine whether IL-18 is an important factor in mediating atherosclerosis during stress. If so, IL-18 is a target for reducing the effects of stress on atherosclerosis. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL088083-01A1
Application #
7386425
Study Section
Special Emphasis Panel (ZRG1-CVS-Q (90))
Program Officer
Rabadan-Diehl, Cristina
Project Start
2008-02-15
Project End
2010-01-31
Budget Start
2008-02-15
Budget End
2009-01-31
Support Year
1
Fiscal Year
2008
Total Cost
$236,250
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Neal, Sonya; Jaeger, Philipp A; Duttke, Sascha H et al. (2018) The Dfm1 Derlin Is Required for ERAD Retrotranslocation of Integral Membrane Proteins. Mol Cell 69:306-320.e4
Oishi, Yumiko; Spann, Nathanael J; Link, Verena M et al. (2017) SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism. Cell Metab 25:412-427
Glass, Christopher K (2015) Genetic and genomic approaches to understanding macrophage identity and function. Arterioscler Thromb Vasc Biol 35:755-62
Marcondes, Maria Cecilia Garibaldi; Zhukov, Viktor; Bradlow, Henry et al. (2011) Effects of chronic mental stress and atherogenic diet on the immune inflammatory environment in mouse aorta. Brain Behav Immun 25:1649-57
Alboni, Silvia; Montanari, Claudia; Benatti, Cristina et al. (2011) Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain. Brain Behav Immun 25:483-93
Alboni, Silvia; Cervia, Davide; Sugama, Shuei et al. (2010) Interleukin 18 in the CNS. J Neuroinflammation 7:9
Cottone, Pietro; Sabino, Valentina; Roberto, Marisa et al. (2009) CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci U S A 106:20016-20
Alboni, Silvia; Cervia, Davide; Ross, Brendon et al. (2009) Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain. J Neuroimmunol 214:43-54
Sanchez-Alavez, Manuel; Criado, Jose R; Klein, Izabella et al. (2008) Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice. Neuroreport 19:1473-7