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慢性不可预测的轻度压力在ApoE小鼠中通过脂肪组织功能障碍促进动脉样硬化
Min Mao1, Yalan Deng1, Li Wang2
1The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, Beijing, China.
PeerJ
|September 11, 2023
概括
慢性不可预测的轻度压力 (CUMS) 通过引起白色脂肪组织 (WAT) 功能障碍而加剧动脉样硬化,导致脂质不良,炎症和胰岛素抵抗. 这项研究强调异常的脂肪功能是将CUMS与动脉样硬化进展联系起来的关键机制.
科学领域:
- 心血管疾病研究研究
- 代谢综合征研究 代谢综合征研究
- 压力和健康调查
背景情况:
- 众所周知,慢性不可预测的轻度压力 (CUMS) 会使动脉样硬化恶化,但根本机制尚未完全理解.
- 脂肪组织作为内分泌器官,在心血管健康中起着至关重要的作用.
- 这项研究调查了CUMS通过诱导白色脂肪细胞缩和功能障碍加剧动脉样硬化症的假设.
研究的目的:
- 阐明CUMS加剧动脉样硬化的机制.
- 调查白脂肪组织 (WAT) 功能障碍在CUMS诱导的动脉样硬化中的作用.
- 确定CUMS相关心血管并发症的潜在治疗点.
主要方法:
- 在食西方饮食的ApoE-/-) 小鼠中建立了一个CUMS诱导的动脉样硬化模型.
- 评估了类似抑郁症的行为,血清脂质概况和生化标志物.
- 分析了动脉样硬化病变,脂肪细胞大小,脂质沉积和脂肪组织中的基因/蛋白质表达.
主要成果:
- 在ApoE-/-小鼠中,CUMS加剧了动脉样硬化病变,减轻了体重,并增加了WAT百分比.
- CUMS导致高密度脂蛋白 (HDL) 水平降低,脂肪细胞缩,以及关键脂肪细胞基因 (例如,Pparg,Slc2a4,Adipoq) 的表达减少.
- 观察到皮下WAT的脂质合成和炎症增加,脂质水解减少,以及HDL相关蛋白ApoA-I的表达减少,以及胰岛素抵抗的恶化.
结论:
- CUMS诱导脂肪组织功能障碍,导致脂质不良,炎症和胰岛素抵抗,从而加剧动脉样硬化.
- 在CUMS下脂肪组织中高脂相关蛋白的表达减少可能会将脂肪细胞缩与晚期动脉样硬化联系起来.
- 这项研究揭示了通过异常的脂肪功能引起的CUMS动脉样硬化的新机制,确定了潜在的治疗标.
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