Dai Yusang, Junho Carolina Victoria Cruz, Schieren Luisa, Wollenhaupt Julia, Sluimer Judith C, van der Vorst Emiel P C, Noels Heidi
Institute for Molecular Cardiovascular Research (IMCAR), University Hospital, RWTH Aachen University, Aachen, Germany.
Physical Examination Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Front Cell Dev Biol. 2024 Aug 12;12:1446964. doi: 10.3389/fcell.2024.1446964. eCollection 2024.
Cell activation and nutrient dysregulation are common consequences of atherosclerosis and its preceding risk factors, such as hypertension, dyslipidemia, and diabetes. These diseases may also impact cellular metabolism and consequently cell function, and the other way around, altered cellular metabolism can impact disease development and progression through altered cell function. Understanding the contribution of altered cellular metabolism to atherosclerosis and how cellular metabolism may be altered by co-morbidities and atherosclerosis risk factors could support the development of novel strategies to lower the risk of CVD. Therefore, we briefly review disease pathogenesis and the principles of cell metabolic pathways, before detailing changes in cellular metabolism in the context of atherosclerosis and comorbidities. In the hypoxic, inflammatory and hyperlipidemic milieu of the atherosclerotic plaque riddled with oxidative stress, metabolism shifts to increase anaerobic glycolysis, the pentose-phosphate pathway and amino acid use. We elaborate on metabolic changes for macrophages, neutrophils, vascular endothelial cells, vascular smooth muscle cells and lymphocytes in the context of atherosclerosis and its co-morbidities hypertension, dyslipidemia, and diabetes. Since causal relationships of specific key genes in a metabolic pathway can be cell type-specific and comorbidity-dependent, the impact of cell-specific metabolic changes must be thoroughly explored , with a focus on also systemic effects. When cell-specific treatments become feasible, this information will be crucial for determining the best metabolic intervention to improve atherosclerosis and its interplay with co-morbidities.
细胞活化和营养失调是动脉粥样硬化及其前期危险因素（如高血压、血脂异常和糖尿病）的常见后果。这些疾病也可能影响细胞代谢，进而影响细胞功能，反之，改变的细胞代谢可通过改变细胞功能影响疾病的发展和进程。了解细胞代谢改变对动脉粥样硬化的作用以及合并症和动脉粥样硬化危险因素如何改变细胞代谢，有助于开发降低心血管疾病风险的新策略。因此，在详细阐述动脉粥样硬化和合并症背景下细胞代谢的变化之前，我们简要回顾疾病发病机制和细胞代谢途径的原理。在充满氧化应激的动脉粥样硬化斑块的缺氧、炎症和高脂血症环境中，代谢转变为增加无氧糖酵解、磷酸戊糖途径和氨基酸利用。我们阐述了动脉粥样硬化及其合并症（高血压、血脂异常和糖尿病）背景下巨噬细胞、中性粒细胞、血管内皮细胞、血管平滑肌细胞和淋巴细胞的代谢变化。由于代谢途径中特定关键基因的因果关系可能具有细胞类型特异性和合并症依赖性，因此必须深入探讨细胞特异性代谢变化的影响，同时关注全身效应。当细胞特异性治疗变得可行时，这些信息对于确定改善动脉粥样硬化及其与合并症相互作用的最佳代谢干预措施至关重要。
