Department of Internal Medicine, University of Cincinnati, Ohio 45267, USA.
Physiol Genomics. 2013 Aug 15;45(16):697-709. doi: 10.1152/physiolgenomics.00042.2013. Epub 2013 Jun 4.
Inflammatory cross talk between perivascular adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We previously reported that human perivascular (PV) adipocytes exhibit a proinflammatory phenotype and less adipogenic differentiation than do subcutaneous (SQ) adipocytes. To gain a global view of the genomic basis of biologic differences between PV and SQ adipocytes, we performed genome-wide expression analyses to identify differentially expressed genes between adipocytes derived from human SQ vs. PV adipose tissues. Although >90% of well-expressed genes were similarly regulated, we identified a signature of 307 differentially expressed genes that were highly enriched for functions associated with the regulation of angiogenesis, vascular morphology, inflammation, and blood clotting. Of the 156 PV upregulated genes, 59 associate with angiogenesis, vascular biology, or inflammation, noteworthy of which include TNFRSF11B (osteoprotegerin), PLAT, TGFB1, THBS2, HIF1A, GATA6, and SERPINE1. Of 166 PV downregulated genes, 21 associated with vascular biology and inflammation, including ANGPT1, ANGPTL1, and VEGFC. Consistent with the emergent hypothesis that PV adipocytes differentially regulate angiogenesis and inflammation, cell culture-derived adipocyte-conditioned media from PV adipocytes strongly enhanced endothelial cell tubulogenesis and monocyte migration compared with media from SQ adipocytes. These findings demonstrate that PV adipocytes have the potential to significantly modulate vascular inflammatory crosstalk in the setting of atherosclerosis by their ability to signal to both endothelial and inflammatory cells.
血管周脂肪组织与血管壁之间的炎症串扰被认为有助于动脉粥样硬化的发病机制。我们之前报道过，人类血管周（PV）脂肪细胞表现出促炎表型，并且比皮下（SQ）脂肪细胞的脂肪生成分化能力更低。为了全面了解 PV 和 SQ 脂肪细胞之间生物学差异的基因组基础，我们进行了全基因组表达分析，以鉴定源自人 SQ 与 PV 脂肪组织的脂肪细胞之间差异表达的基因。虽然 >90%高表达的基因表达模式相似，但我们鉴定出了一个 307 个差异表达基因的特征签名，这些基因高度富集与血管生成、血管形态、炎症和血液凝固的调节相关的功能。在 156 个上调的 PV 基因中，有 59 个与血管生成、血管生物学或炎症相关，其中包括 TNFRSF11B（骨保护素）、PLAT、TGFB1、THBS2、HIF1A、GATA6 和 SERPINE1。在 166 个下调的 PV 基因中，有 21 个与血管生物学和炎症相关，包括 ANGPT1、ANGPTL1 和 VEGFC。与 PV 脂肪细胞通过其向内皮细胞和炎症细胞发出信号的能力，能够差异化地调节血管生成和炎症的新兴假说一致，来自 PV 脂肪细胞的细胞培养衍生的脂肪细胞条件培养基与来自 SQ 脂肪细胞的培养基相比，强烈增强了内皮细胞小管形成和单核细胞迁移。这些发现表明，PV 脂肪细胞具有通过其向内皮细胞和炎症细胞发出信号的能力，在动脉粥样硬化的情况下，能够显著调节血管炎症串扰。
