Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H₂O₂− or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H₂O₂− or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.

腹主动脉瘤（AAA）是一种危险的血管疾病，迄今为止尚无任何有效的药物治疗方法。新的证据表明，主动脉区域之间血管周围脂肪组织（PVAT）的表型差异与动脉粥样硬化的发展有关，大型动物和人类的腹主动脉比胸主动脉更容易发生动脉粥样硬化。胸主动脉瘤（TAA）的患病率远低于腹主动脉瘤（AAA）。在本研究中，我们研究了胸腔PVAT（T-PVAT）移植对主动脉瘤形成的影响以及T-PVAT对血管平滑肌细胞的影响。建立磷酸钙诱导的小鼠AAA模型。在去除内源性腹部 PVAT (A-PVAT) 并进行磷酸钙治疗后，将 T-PVAT (20 mg) 植入受体小鼠的腹主动脉周围。术后两周处死小鼠，测量肾下主动脉最大外径。我们发现 T-PVAT 比 A-PVAT 显示出更像 BAT 的表型；与假手术对照或 A-PVAT 移植相比，T-PVAT 移植显着减弱了磷酸钙诱导的腹主动脉扩张和弹性退化。此外，T-PVAT移植很大程度上保留了腹主动脉壁中的平滑肌细胞含量。 T-PVAT 与血管平滑肌细胞 (VSMC) 共培养显着抑制 H ₂ O ₂ - 或 TNFα 加放线菌酮诱导的 VSMC 凋亡。 RNA测序分析表明，T-PVAT富含褐变脂肪细胞和抗凋亡分泌蛋白。 我们进一步证实，从 T-PVAT 中分离的成熟脂肪细胞的分泌组显着抑制 H ₂ O ₂ - 或 TNFα 加放线菌酮诱导的 VSMC 凋亡。通过蛋白质组学和生物信息学分析，我们确定软骨寡聚基质蛋白 (COMP) 作为一种分泌蛋白，在 T-PVAT 中显着增加。重组COMP蛋白显着抑制VSMC凋亡。我们得出结论，T-PVAT 对 VSMC 发挥抗凋亡作用并减弱 AAA 形成，这可能归因于褐变脂肪细胞的分泌组。