Atherosclerosis-related cardiovascular diseases are a major cause of death globally, and are expected to increase in prevalence with the rising incidence of obesity and type 2 diabetes mellitus. Despite being very common, there are still large knowledge gaps in our understanding of how atherosclerosis develops. Furthermore, most animal models for atherosclerosis rely on the use of a continuous high-fat diet (HFD), which does not represent the typical human experience of varied dietary intakes over the life course. Two studies published in Nature have now developed new models that reveal novel insights into the development of atherosclerotic plaques.

The mice on the alternating HFD had significantly worse development of atherosclerosis than the control group mice. The alternating HFD led to a quicker development of atherosclerosis, and the plaques at several sites were larger than those in the control mice. “Initial exposure to the HFD triggers the reprogramming of myeloid progenitors in the bone marrow, which, upon re-exposure, leads to emergency myelopoiesis (that is, a rapid and enhanced production of myeloid cells, typically observed in response to stress, infection, inflammation or injury),” says Ait-Oufella. The researchers were able to demonstrate that neutrophils derived from the bone marrow entered the bloodstream; these cells then infiltrated the arterial walls, where they exacerbated atherosclerosis.

动脉粥样硬化相关的心血管疾病是全球死亡的主要原因，预计随着肥胖和 2 型糖尿病发病率的上升，患病率将会增加。尽管非常普遍，但我们对动脉粥样硬化如何发展的理解仍然存在很大的知识空白。此外，大多数动脉粥样硬化的动物模型依赖于连续高脂饮食 （HFD） 的使用，这并不代表人类在生命过程中摄入不同饮食的典型体验。发表在《自然》杂志上的两项研究现在开发了新模型，揭示了对动脉粥样硬化斑块发展的新见解。

交替 HFD 组小鼠动脉粥样硬化的发生明显低于对照组小鼠。交替的 HFD 导致动脉粥样硬化发展更快，并且多个部位的斑块比对照小鼠的斑块大。“最初接触 HFD 会触发骨髓中骨髓祖细胞的重编程，再次暴露后，会导致紧急骨髓生成（即骨髓细胞的快速和增强产生，通常在响应压力、感染、炎症或损伤时观察到），”Ait-Oufella 说。研究人员能够证明来自骨髓的中性粒细胞进入血液;然后这些细胞浸润动脉壁，加剧动脉粥样硬化。