Biessen Erik A L, Wouters Kristiaan
aDepartment of Pathology bDepartment of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands cInstitute for Molecular Cardiovascular Research (IMCAR), University Hospital RWTH, Aachen, Aachen, Germany.
Curr Opin Lipidol. 2017 Oct;28(5):419-426. doi: 10.1097/MOL.0000000000000447.
The pivotal role of macrophages in experimental atherosclerosis is firmly established, but their contribution to human disease is less well defined. In this review we have outlined the current insights on macrophage phenotypes and their presumed precursors, monocytes, in clinical atherosclerosis, and their association with disease progression. Moreover, we will assess major clinical modifiers of macrophage-mediated plaque inflammation and define the outstanding questions for further study.
Our survey indicates that macrophage accumulation and status in human plaques are linked with lesion progression and destabilization as well as with symptomatic coronary artery disease. Likewise, levels of their precursors, circulating monocytes were repeatedly seen to associate with atherosclerosis and to predict clinical outcome. Furthermore, the presence and phenotype of both macrophages and monocytes appears to be responsive to the traditional risk factors of atherosclerosis, including hypercholesterolemia, hypertension, and type 2 diabetes, and to treatment thereof, with clear repercussions on disease development.
Although plaque macrophages and their precursor cells do represent attractive targets for treating cardiovascular diseases, this therapeutic avenue requires much deeper understanding of the complexity of macrophage biology in human atherosclerosis than available at present.
巨噬细胞在实验性动脉粥样硬化中的关键作用已得到明确证实，但其对人类疾病的贡献尚不太明确。在本综述中，我们概述了目前对临床动脉粥样硬化中巨噬细胞表型及其假定前体单核细胞的认识，以及它们与疾病进展的关联。此外，我们将评估巨噬细胞介导的斑块炎症的主要临床调节因素，并确定有待进一步研究的突出问题。
我们的调查表明，人类斑块中巨噬细胞的积聚和状态与病变进展、不稳定以及有症状的冠状动脉疾病有关。同样，其前体循环单核细胞的水平也多次被发现与动脉粥样硬化相关，并可预测临床结果。此外，巨噬细胞和单核细胞的存在及表型似乎对动脉粥样硬化的传统危险因素（包括高胆固醇血症、高血压和2型糖尿病）及其治疗有反应，对疾病发展有明显影响。
尽管斑块巨噬细胞及其前体细胞确实是治疗心血管疾病的有吸引力的靶点，但这条治疗途径需要比目前更深入地了解人类动脉粥样硬化中巨噬细胞生物学的复杂性。
