Perivascular adipose tissue inflammation in abdominal aortic aneurysm: An underrecognized contributor

Figures

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  Figure 1. Distribution of PVAT inflammatory cells and main actors at each stage. Obesity and smoking are triggers for PVAT inflammation. Neutrophils may participate in early inflammation. Endothelial cells and mast cells can both promote the movement of monocytes from the circulation into PVAT. Proinflammatory macrophages can interact with adipocytes through inflammatory factors and adipokines, contributing to continuous aggravation of inflammation. T/B lymphocytes and adipose tissue dendritic cells also assist in this process. During later phases, macrophage phenotypes may shift toward reparative states, while trained-immunity-associated epigenetic changes may contribute to persistent inflammatory responses. Excessive MMPs often lead to the degradation of elastic fibers, and the inflammatory microenvironment can also cause the loss of smooth muscle cells. Abbreviations: MMP, matrix metalloproteinase; PVAT, perivascular adipose tissue; SMC, smooth muscle cell.

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  Figure 2. Mechanisms of PVAT inflammation promoting AAA. Macrophage-derived MMPs contribute importantly to ECM degradation: endothelial cells secrete ET-1 to promote macrophage recruitment and increase MMP-2. Mast cells increase MMP-9 through IFN-γ signaling. CCL2 can be secreted by adipocytes, and macrophages derived from this mainly secrete MMP-12. Overexpression of OPN in adipocytes enhances MMP-9 and MMP-12. PDGF-D secreted by adipocytes increases macrophage infiltration and stimulates fibroblast activation through TGF-β/Smad. EVs secreted by adipocytes promote the proliferation and migration of vascular smooth muscle cells. Both visfatin and adipocyte-derived leptin promote phenotypic transformation of VSMCs through the MAPK pathway. IL-6 upregulates AT1 receptor expression, thereby enhancing Ang Ⅱ signaling and ROS production, which ultimately promotes VSMC apoptosis. A decrease in adiponectin can also increase ROS. In the cited AAA mouse model, abdominal PVAT showed reduced COMP compared with thoracic PVAT; COMP may protect VSMCs from apoptosis by increasing survivin. Apoptosis of VSMCs can promote inflammation in turn through CCL2. Abbreviations: Ang Ⅱ, angiotensin Ⅱ; CCL2, C-C…

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  Figure 3. Graphical summary. This figure summarizes the contribution of PVAT-derived inflammation to the progression of abdominal aortic aneurysm, and its potential implications for clinical translation. Abbreviations: CCL2, C-C motif chemokine ligand 2; ECM, extracellular matrix; IL-6, interleukin-6; MMP, matrix metalloproteinase; PVAT, perivascular adipose tissue; TNF-α, tumor necrosis factor-α; VSMC, vascular smooth muscle cell.