STAT4 contributes to adipose tissue inflammation and atherosclerosis.
Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4(-/-)Apoe(-/-) mice and Apoe(-/-) controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4(-/-)Apoe(-/-) and Apoe(-/-) mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe(-/-) mice. In contrast, in Stat4(-/-)Apoe(-/-) mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4(-/-)Apoe(-/-) mice. Importantly, Stat4(-/-)Apoe(-/-) mice on a Western diet had significantly reduced plaque burden vs Apoe(-/-) controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation.
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA dobriaad@evms.edu.
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AD
Dobrian
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
M A
MA
Hatcher
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
J J
JJ
Brotman
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
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EV
Galkina
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
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Taghavie-Moghadam
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
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H
Pei
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
B A
BA
Haynes
Departments of Physiological SciencesMicrobiology and Molecular Cell BiologyInternal MedicineEastern Virginia Medical School, 700W Olney Road, Norfolk, Virginia 23505, USADivision of Inflammation BiologyLa Jolla Institute for Allergy and Immunology, San Diego, La Jolla, California, USA.
J L
JL
Nadler
D000818:Animals; D001011:Aorta; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016764:Cell Polarity; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects; D005260:Female; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018345:Mice, Knockout; D010053:Ovary; D015434:Panniculitis / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D050797:STAT4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms
D001057:Apolipoproteins E; D018925:Chemokines; D016207:Cytokines; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse
T lymphocytes; chemokines; macrophages; peri-aortic fat