Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
Department of Human Physiology, University of Oregon, Eugene, Oregon, USA.
Sci Rep. 2019 Feb 27;9(1):2925. doi: 10.1038/s41598-019-39466-x.
Atherogenic remodeling often occurs at arterial locations with disturbed blood flow (i.e., low or oscillatory) and both aging and western diet (WD) increase the likelihood for pro-atherogenic remodeling. However, it is unknown if old age and/or a WD modify the pro-atherogenic response to disturbed blood flow. We induced disturbed blood flow by partial carotid ligation (PCL) of the left carotid artery in young and old, normal chow (NC) or WD fed male B6D2F1 mice. Three weeks post-PCL, ligated carotid arteries had greater intima media thickness, neointima formation, and macrophage content compared with un-ligated arteries. WD led to greater remodeling and macrophage content in the ligated artery compared with NC mice, but these outcomes were similar between young and old mice. In contrast, nitrotyrosine content, a marker of oxidative stress, did not differ between WD and NC fed mice, but was greater in old compared with young mice in both ligated and un-ligated carotid arteries. In primary vascular smooth muscle cells, aging reduced proliferation, whereas conditioned media from fatty acid treated endothelial cells increased proliferation. Taken together, these findings suggest that the remodeling and pro-inflammatory response to disturbed blood flow is increased by WD, but is not increased by aging.
动脉粥样硬化性重塑通常发生在血流紊乱(即低流或振荡)的动脉部位,衰老和西方饮食(WD)都会增加促动脉粥样硬化性重塑的可能性。然而,尚不清楚衰老和/或 WD 是否会改变对血流紊乱的促动脉粥样硬化反应。我们通过对年轻和老年、正常饮食(NC)或 WD 喂养的雄性 B6D2F1 小鼠的左侧颈总动脉进行部分结扎(PCL)来诱导血流紊乱。PCL 后 3 周,与未结扎动脉相比,结扎的颈动脉有更大的内膜中膜厚度、新生内膜形成和巨噬细胞含量。与 NC 小鼠相比,WD 导致结扎动脉的重塑和巨噬细胞含量增加,但在年轻和老年小鼠之间这些结果相似。相比之下,硝基酪氨酸含量(氧化应激的标志物)在 WD 和 NC 喂养的小鼠之间没有差异,但在结扎和未结扎的颈动脉中,老年小鼠的含量均高于年轻小鼠。在原代血管平滑肌细胞中,衰老会降低增殖能力,而脂肪酸处理的内皮细胞的条件培养基会增加增殖能力。综上所述,这些发现表明,WD 会增加对血流紊乱的重塑和促炎反应,但不会随衰老而增加。