Division of Cardiology, Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan 330, Taiwan.
School of Medicine, National Defense Medical Center, Taipei 114, Taiwan.
Int J Mol Sci. 2023 Mar 16;24(6):5669. doi: 10.3390/ijms24065669.
Bariatric surgery reduces body weight, enhances metabolic and diabetic control, and improves outcomes on obesity-related comorbidities. However, the mechanisms mediating this protection against cardiovascular diseases remain unclear. We investigated the effect of sleeve gastrectomy (SG) on vascular protection in response to shear stress-induced atherosclerosis using an overweighted and carotid artery ligation mouse model. Eight-week-old male wild-type mice (C57BL/6J) were fed a high-fat diet (HFD) for two weeks to induce weight gain and dysmetabolism. SG was performed in HFD-fed mice. Two weeks after the SG procedure, partial carotid-artery ligation was performed to promote disturbed flow-induced atherosclerosis. Compared with the control mice, HFD-fed wild-type mice exhibited increased body weight, total cholesterol level, hemoglobin A1c, and enhanced insulin resistance; SG significantly reversed these adverse effects. As expected, HFD-fed mice exhibited greater neointimal hyperplasia and atherosclerotic plaques than the control group, and the SG procedure attenuated HFD-promoted ligation-induced neointimal hyperplasia and arterial elastin fragmentation. Besides, HFD promoted ligation-induced macrophage infiltration, matrix metalloproteinase-9 expression, upregulation of inflammatory cytokines, and increased vascular endothelial growth factor secretion. SG significantly reduced the above-mentioned effects. Moreover, HFD restriction partially reversed the intimal hyperplasia caused by carotid artery ligation; however, this protective effect was significantly lower than that observed in SG-operated mice. Our study demonstrated that HFD deteriorates shear stress-induced atherosclerosis and SG mitigates vascular remodeling, and this protective effect was not comparable in HFD restriction group. These findings provide a rationale for using bariatric surgery to counter atherosclerosis in morbid obesity.
减重手术可减轻体重、改善代谢和糖尿病控制,并改善肥胖相关合并症的结局。然而,介导这种对心血管疾病的保护作用的机制仍不清楚。我们使用超重和颈动脉结扎小鼠模型,研究了袖状胃切除术(SG)对剪切应力诱导的动脉粥样硬化的血管保护作用。8 周龄雄性野生型小鼠(C57BL/6J)用高脂肪饮食(HFD)喂养两周以诱导体重增加和代谢紊乱。在 HFD 喂养的小鼠中进行 SG。SG 手术后两周,进行部分颈动脉结扎以促进血流紊乱诱导的动脉粥样硬化。与对照组相比,HFD 喂养的野生型小鼠表现出体重增加、总胆固醇水平升高、糖化血红蛋白升高和胰岛素抵抗增强;SG 显著逆转了这些不利影响。正如预期的那样,HFD 喂养的小鼠表现出比对照组更大的新生内膜增生和动脉粥样硬化斑块,SG 程序减轻了 HFD 促进的结扎诱导的新生内膜增生和动脉弹性蛋白碎片化。此外,HFD 促进了结扎诱导的巨噬细胞浸润、基质金属蛋白酶-9 表达、炎症细胞因子的上调和血管内皮生长因子的分泌。SG 显著降低了上述效应。此外,HFD 限制部分逆转了颈动脉结扎引起的内膜增生;然而,这种保护作用明显低于 SG 手术组。我们的研究表明,HFD 会使剪切应力诱导的动脉粥样硬化恶化,而 SG 减轻血管重塑,并且在 HFD 限制组中这种保护作用不可比。这些发现为使用减重手术来对抗病态肥胖引起的动脉粥样硬化提供了依据。