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Early‐life Stress Induces Dysregulated Heme Homeostasis and Pro‐inflammatory Phenotype in Adult Male Mice
Author(s) -
Ho Dao,
Pettway Yasminye,
Burch Mariah,
Pollock Jennifer
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.811.12
Subject(s) - endocrinology , medicine , hemopexin , haptoglobin , immunostaining , acute phase protein , inflammation , proinflammatory cytokine , heme , chemistry , biochemistry , enzyme , immunohistochemistry
Early‐life stress (ELS) is a major independent risk factor for cardiovascular disease (CVD). Recently, inflammatory acute‐phase response (APR) proteins have been identified as novel markers of CVD; however, it is unknown whether ELS induces APR. We hypothesized that ELS induces vascular dysfunction and dysregulation of APR proteins. Utilizing adult male control mice and mice exposed to maternal separation with early weaning (MSEW), an ELS model, we determined vascular function and macrophage infiltration as well as levels of inflammatory and acute‐phase proteins. MSEW mice displayed aortic endothelial dysfunction as evidenced by blunted acetylcholine relaxation (wire myography; 67.6 ± 5.8 vs 89.9 ± 2.7 % relaxation, p = 0.01) and increased aortic adventitial macrophage infiltration (F4/80 immunostaining; 7.0 ± 2.2 vs 2.8 ± 2.3 cells/mm 2 , p < 0.01). MSEW mice also showed increased plasma cytokines (sICAM, 406.2 ± 23.1 vs 333.5 ± 19.4 ng/ml; p = 0.03; mCSF, 945.3 ± 65.4 vs 737.4 ± 19.6 pg/ml; p = 0.01), plasma heme (23.3 ± 1.9 vs 18.2 ± 1.4 μM, p = 0.04), and plasma haptoglobin (14.2 ± 4.8 vs 3.0 ± 7.7 μg/ml, p = 0.03). Conversely, in the spleen of MSEW mice, haptoglobin was significantly decreased (6.8 ± 0.5 vs 13.0 ± 2.1 ng/mg protein, p = 0.007) as well as expression of the heme‐degrading protein, heme oxygenase‐1 (0.90 ± 0.05 fold change from control, p = 0.03). Plasma and liver hemopexin levels were not significantly different between groups. These data indicate that ELS induces a pro‐oxidant and pro‐inflammatory vascular phenotype in MSEW mice with dysregulation of heme homeostasis. APS STEP‐UP to YP, NIH F32 HL116145 to DHH, and NIH P01HL69999 to JSP.