Tran Vivian, Brettle Holly, Diep Henry, Figueiredo Galvao Hericka Bruna, Fanson Kerry V, Sobey Christopher G, Drummond Grant R, Vinh Antony, Jelinic Maria
Department of Microbiology, Anatomy Physiology and Pharmacology, Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, Victoria, Australia.
Department of Animal, Plant and Soil Sciences, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, Victoria, Australia.
FASEB J. 2025 Mar 15;39(5):e70413. doi: 10.1096/fj.202401871R.
Perivascular adipose tissue (PVAT) expansion promotes inflammation and vascular dysfunction in metabolic syndrome (MetS), but the sexual dimorphisms of PVAT are poorly understood. Using a new mouse model of diet-induced MetS, we characterized the aorta and determined the influence of PVAT on vascular function in males and females. Six-week-old C57BL/6 mice were fed either a high-fat diet (43% kcal in food) with high sugar and salt in their drinking water (10% high fructose corn syrup and 0.9% NaCl; HFSS), or a normal chow diet (NCD) for 10 weeks. The aorta was characterized at endpoint using pin myography, flow cytometry, bulk RNA-sequencing, GSEA analysis, and histology. Compared to NCD-fed mice, HFSS-fed mice displayed higher weight gain, fasting blood glucose, systolic blood pressure, aortic fibrosis, and perivascular adipocyte cross-sectional area, regardless of sex (p < .05). Circulating adiponectin levels were also higher in HFSS-fed males compared to NCD males. PVAT enhanced U46619-mediated contraction in HFSS males only. HFSS increased the expression of immune regulation genes in female PVAT and ion transport genes in male PVAT but had no effect on total numbers of immune cells in the aorta in either sex. Despite having similar effects on metabolic parameters in males and females, HFSS caused contrasting effects on vascular function with and without PVAT. These data highlight the sexual dimorphisms of PVAT in regulating the vasculature in healthy and diseased states.
血管周围脂肪组织（PVAT）扩张会促进代谢综合征（MetS）中的炎症和血管功能障碍，但PVAT的性别差异却鲜为人知。我们使用一种新的饮食诱导型MetS小鼠模型，对主动脉进行了表征，并确定了PVAT对雄性和雌性血管功能的影响。六周龄的C57BL/6小鼠被喂食高脂饮食（食物中43%千卡热量），饮用水中含有高糖和高盐（10%高果糖玉米糖浆和0.9%氯化钠；HFSS），或正常的普通饮食（NCD），持续10周。在实验终点，使用血管张力描记法、流式细胞术、批量RNA测序、基因集富集分析（GSEA）和组织学对主动脉进行表征。与喂食NCD的小鼠相比，无论性别如何，喂食HFSS的小鼠体重增加、空腹血糖、收缩压、主动脉纤维化和血管周围脂肪细胞横截面积均更高（p<0.05）。与NCD雄性小鼠相比，喂食HFSS的雄性小鼠循环脂联素水平也更高。PVAT仅增强了喂食HFSS的雄性小鼠中U46619介导的收缩。HFSS增加了雌性PVAT中免疫调节基因的表达以及雄性PVAT中离子转运基因的表达，但对两性主动脉中免疫细胞的总数均无影响。尽管HFSS对雄性和雌性的代谢参数有相似的影响，但在有或没有PVAT的情况下，HFSS对血管功能产生了相反的影响。这些数据突出了PVAT在健康和疾病状态下调节血管系统中的性别差异。
