Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue

Figures

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  Figure 1. Correlation between abdominal perimeter (A), body mass index (BMI) (B), the macrophage marker CD68 (C), the T lymphocyte markers CD3 (D), CD4 (E), and CD8 (F), leptin (G), and adiponectin (H) and G protein-coupled receptor kinase 2 (GRK2) mRNA in human aortic perivascular adipose tissue. Univariate association was performed by Spearman correlation test. AU: arbitrary units.

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  Figure 2. Concentration-response curves to acetylcholine (ACh (A,B)), insulin (C,D) and diethylamine NONOate (DEA-NO (E,F)) in aorta segments with perivascular adipose tissue (PVAT+) or without (PVAT-) from control and LysM-GRK2+/− mice fed on normal diet (ND) or high (HFD) fat diet (n = 7–19); * p < 0.05 vs. PVAT−, # vs. control mice, by two-way ANOVA.

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  Figure 3. Maximum response induced by 120 mmol/L K+ solution (A,B) and concentration-response curves to phenylephrine (Phe; (C,D)), in aorta segments with perivascular adipose tissue (PVAT+) or without (PVAT−) from control and LysM-GRK2+/− mice fed on normal (ND) or high (HFD) fat diet (n = 9–17); * p < 0.05 vs. PVAT− by unpaired t-test (A,B).

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  Figure 4. mRNA expression of tumor necrosis factor-α (TNFα) (A), the NADPH oxidase (Nox) subunit Nox1 (B), IL6 (C), microsomal prostaglandin E synthase (mPGES-1 (D) and adiponectin (E) in aortic perivascular adipose tissue from control and LysM-GRK2+/− mice fed on normal (ND) or high (HFD) fat diet. * p < 0.05 vs. ND, # vs. control mice by Mann–Whitney or unpaired t-test when normality is reached (by Shapiro–Wilk). (F) Concentration-response curves to insulin in aorta segments with perivascular adipose tissue (PVAT+) in the absence or in the presence of an anti-TNFα antibody or the specific Nox1 inhibitor NOXA1ds from control mice fed on high fat diet (HFD) (n = 4–5); * p < 0.05 vs. arteries in the absence of inhibitors by two-way ANOVA.

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  Figure 5. mRNA expression of F4/80 (A) and CD3 (B) in aortic PVAT from control and LysM-GRK2+/− mice fed a normal (ND) or a high fat diet (HFD). * p < 0.05 vs. ND by Mann–Whitney or unpaired t-test when normality is reached (by Shapiro–Wilk).

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  Figure 6. Schematic representation of the correlation of GRK2 levels with inflammatory markers in human PVAT and of the effects of downregulating GRK2 in myeloid cells for the vascular responses in vessels with PVAT after the induction of obesity.