Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
The Finsen Laboratory, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2022 Jul 28;12(1):12931. doi: 10.1038/s41598-022-16846-4.
Testosterone deficiency in men is associated with increased atherosclerosis burden and increased cardiovascular risk. In male mice, testosterone deficiency induced by castration increases atherosclerosis as well as mature B cell numbers in spleen. As B cells are potentially pro-atherogenic, we hypothesized that there may be a link between these effects. To address whether mature B cell deficiency alter the atherogenic response to castration, we studied B cell-deficient μMT and genotype control male mice on an atherosclerosis-prone Apoe background that were castrated or sham-operated pre-pubertally and fed a high-fat diet between 8 and 16 weeks of age to accelerate atherosclerosis development. Genotype did not affect the effects of castration on body weight or weights of fat depots and there were no differences in serum cholesterol levels across the four groups. Atherosclerosis assessed by quantification of lesion area in serial sections of the aortic root was significantly increased by castration and by the μMT mutation, with no significant interaction between genotype and surgery. In conclusion, castration evokes a similar atherogenic response in B cell-deficient μMT and control mice. These data suggest that atherogenesis following castration is unrelated to the effects of androgens on mature B cell numbers.
男性睾酮缺乏与动脉粥样硬化负担增加和心血管风险增加有关。在雄性小鼠中，去势引起的睾酮缺乏会增加动脉粥样硬化以及脾脏中成熟 B 细胞的数量。由于 B 细胞具有潜在的促动脉粥样硬化作用，我们假设这两种效应之间可能存在联系。为了确定成熟 B 细胞缺陷是否改变去势对动脉粥样硬化的反应，我们研究了易患动脉粥样硬化的 Apoe 背景下的 B 细胞缺陷 μMT 和基因型对照雄性小鼠，这些小鼠在青春期前被去势或假手术，并在 8 至 16 周龄时接受高脂肪饮食喂养，以加速动脉粥样硬化的发展。基因型不影响去势对体重或脂肪组织重量的影响，四组之间的血清胆固醇水平也没有差异。通过对主动脉根部连续切片中病变面积的定量评估，动脉粥样硬化明显增加由去势和 μMT 突变引起，基因型和手术之间没有明显的相互作用。总之，去势在 B 细胞缺陷 μMT 和对照小鼠中引起相似的促动脉粥样硬化反应。这些数据表明，去势后动脉粥样硬化的发生与雄激素对成熟 B 细胞数量的影响无关。
