Adipose Inflammation Initiates Recruitment of Leukocytes to Mouse Femoral Artery: Role of Adipo-Vascular Axis in Chronic Inflammation

Abstract

BackgroundAlthough inflammation within adipose tissues is known to play a role in metabolic syndrome, the causative connection between inflamed adipose tissue and atherosclerosis is not fully understood. In the present study, we examined the direct effects of adipose tissue on macro-vascular inflammation using intravital microscopic analysis of the femoral artery after adipose tissue transplantation.Methods and ResultsWe obtained subcutaneous (SQ) and visceral (VIS) adipose tissues from C57BL/6 mice fed normal chow (NC) or a high fat diet (HF), then transplanted the tissues into the perivascular area of the femoral artery of recipient C57/BL6 mice. Quantitative intravital microscopic analysis revealed an increase in adherent leukocytes after adipose tissue transplantation, with VIS found to induce significantly more leukocyte accumulation as compared to SQ. Moreover, adipose tissues from HF fed mice showed significantly more adhesion to the femoral artery. Simultaneous flow cytometry demonstrated upregulation of CD11b on peripheral granulocyte and monocytes after adipose tissue transplantation. We also observed dominant expressions of the inflammatory cytokine IL-6, and chemokines MCP-1 and MIP-1β in the stromal vascular fraction (SVF) of these adipose tissues as well as sera of recipient mice after transplantation. Finally, massive accumulations of pro-inflammatory and dendritic cells were detected in mice with VIS transplantation as compared to SQ, as well as in HF mice as compared to those fed NC.ConclusionOur in vivo findings indicate that adipose tissue stimulates leukocyte accumulation in the femoral artery. The underlying mechanisms involve upregulation of CD11b in leukocytes, induction of cytokines and chemokines, and accumulation of pro-inflammatory cells in the SVF.

Loss of Perivascular Adipose Tissue on Peroxisome Proliferator–Activated Receptor-γ Deletion in Smooth Muscle Cells Impairs Intravascular Thermoregulation and Enhances Atherosclerosis

“…However, the biology, physiology, and pathology of PVAT are unclear. Published data showing a proinflammatory phenotype in PVAT following vascular injury 28, 29 , along with reported secretion of several adipokines/cytokines from PVAT 15 , led to the hypothesis that PVAT may contribute to the development of atherosclerosis 30, 31 . However, there is no experimental evidence to support that PVAT contributes to atherosclerosis.…”

Assessment of Global Cardiac Uptake of Radiolabeled Iron Oxide Nanoparticles in Apolipoprotein-E-Deficient Mice: Implications for Imaging Cardiovascular Inflammation

“…First, there is a report indicating leukocyte recruitment to the arterial wall of 57BL/6 mice, which was not related to atherosclerosis process [40]. Since we did not employ an apoE−/− mice model that were on a normal diet, we cannot exclude the possibility of non-atherosclerosis artery inflammation based on this design and further studies will be required to determine the differential effects of the high-fat western and normal diets on the apoE−/− mice.…”

Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation

“…Leukocyte adhesion in the femoral artery was assessed 3 h after this treatment by intravital microscopy (IVM) as previously described 23,[29][30][31][32][33] . In brief, mice were injected via the left femoral vein with rhodamine 6G chloride (Molecular Probes, Eugene, OR) to label leukocytes in vivo.…”

“…To determine the physiological role of AhR, we investigated the effect of endothelial cell-specific AhR deficiency on the indoxyl sulfate-enhanced leukocyteendothelial interactions using an IVM system 23,[29][30][31][32][33] . First, we purified endothelial cells from lungs taken from AhR fl/fl and eAhR KO mice to confirm the expression of AhR.…”