Department of Medicine, Leon H. Charney Division of Cardiology, Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, New York.
Department of Genetics & Genomic Sciences, Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
J Am Coll Cardiol. 2018 Oct 30;72(18):2181-2197. doi: 10.1016/j.jacc.2018.08.2147.
Atherosclerosis is characterized by the retention of modified lipoproteins in the arterial wall. These modified lipoproteins activate resident macrophages and the recruitment of monocyte-derived cells, which differentiate into mononuclear phagocytes that ingest the deposited lipoproteins to become "foam cells": a hallmark of this disease. In this Part 2 of a 4-part review series covering the macrophage in cardiovascular disease, we critically review the contributions and relevant pathobiology of monocytes, macrophages, and foam cells as relevant to atherosclerosis. We also review evidence that via various pathways, a failure of the resolution of inflammation is an additional key aspect of this disease process. Finally, we consider the likely role played by genomics and biological networks in controlling the macrophage phenotype in atherosclerosis. Collectively, these data provide substantial insights on the atherosclerotic process, while concurrently offering numerous molecular and genomic candidates that appear to hold great promise for selective targeting as clinical therapies.
动脉粥样硬化的特征是修饰后的脂蛋白在动脉壁中的蓄积。这些修饰后的脂蛋白激活了常驻巨噬细胞和单核细胞衍生细胞的募集，这些细胞分化为单核吞噬细胞，吞噬沉积的脂蛋白，成为“泡沫细胞”：这种疾病的一个标志。在涵盖心血管疾病中巨噬细胞的 4 部分综述系列的第 2 部分中，我们批判性地回顾了单核细胞、巨噬细胞和泡沫细胞的贡献及其相关病理生理学，这些与动脉粥样硬化有关。我们还回顾了证据表明，通过各种途径，炎症的消退失败是该疾病过程的另一个关键方面。最后，我们考虑了基因组学和生物网络在控制动脉粥样硬化中巨噬细胞表型方面可能发挥的作用。总的来说，这些数据为动脉粥样硬化过程提供了大量的见解，同时提供了许多分子和基因组候选物，这些候选物似乎为作为临床治疗的选择性靶向提供了巨大的希望。
