Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of cholesterol-laden macrophages at susceptible sites in the artery wall. Altered cellular metabolism plays an important role in the conversion of a macrophage into a lipid-laden foam cell and also in the ability of the macrophage to mount an inflammatory response. In the atherosclerotic lesion environment, the macrophage is exposed to a plethora of extracellular molecules that govern its phenotype, including cytokines, modified lipids, nutrients, and extracellular matrix components. Intracellular metabolic sensors allow the macrophage to adjust to the lesional environment and to alter its cellular functions accordingly. The molecular mechanisms underlying pathophysiological changes in the metabolism sensing machinery are not fully understood. In the current issue of Circulation Research ,1 Liu et al enhance our understanding of foam cell formation by reporting that loss of expression of the metabolic sensor LKB1 (liver kinase B1) in macrophages results in increased uptake of modified lipoproteins, increased foam cell formation, and subsequently, increased atherosclerosis in 2 different mouse models. This study provides new links between macrophage metabolic sensing and atherosclerosis. Article, see p 1047 LKB1, also known as STK11 (serine/threonine kinase 11), is a kinase originally identified as a tumor suppressor in patients with Peutz–Jeghers syndrome—an autosomal dominant genetic disorder associated with increased risk of developing cancer in the gastrointestinal tract and other organs.2 Later studies revealed that LKB1 acts in part as an upstream activator of AMPK (AMP-activated protein kinase)—an intracellular energy sensor activated by low nutrient status in cells as a mechanism to preserve energy.3 However, LKB1 also has AMPK-independent targets in cells. Recent studies have shown that the LKB1/AMPK pathway is activated by glucose deprivation and that reduced levels of the glycolytic intermediate fructose-1,6-bisphosphate …

中文翻译：

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肝激酶B1链接巨噬细胞代谢传感和动脉粥样硬化。

动脉粥样硬化是一种慢性炎性疾病，其特征是在动脉壁的易感部位积累了胆固醇的巨噬细胞。改变的细胞代谢在巨噬细胞向载脂泡沫细胞的转化以及巨噬细胞发炎反应的能力中起重要作用。在动脉粥样硬化病变环境中，巨噬细胞暴露于控制其表型的大量细胞外分子，包括细胞因子，修饰的脂质，营养物质和细胞外基质成分。细胞内代谢传感器可使巨噬细胞适应病变环境并相应地改变其细胞功能。代谢传感机制中病理生理变化的分子机制尚未完全清楚。在本期Circulation Research中，1 Liu等人报道了巨噬细胞中代谢传感器LKB1（肝激酶B1）的表达缺失会导致修饰的脂蛋白摄取增加，泡沫细胞形成增加，从而增强了我们对泡沫细胞形成的理解，随后，在2种不同的小鼠模型中动脉粥样硬化增加。这项研究提供了巨噬细胞代谢感测与动脉粥样硬化之间的新链接。文章，见第1047页LKB1，也称为STK11（丝氨酸/苏氨酸激酶11），是一种最初被鉴定为Peutz-Jeghers综合征患者的肿瘤抑制因子的激酶。胃肠道等器官。2后来的研究表明，LKB1部分充当AMPK（AMP激活的蛋白激酶）的上游激活剂，这是一种细胞内能量传感器，由于细胞中的低营养状态而被激活，从而可以保持能量。3靶细胞。最近的研究表明，LKB1 / AMPK途径被葡萄糖剥夺激活，糖酵解中间体果糖1,6-二磷酸的水平降低了……