Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Trends Cardiovasc Med. 2022 Nov;32(8):525-533. doi: 10.1016/j.tcm.2021.08.015. Epub 2021 Sep 5.
Mounting scientific evidence over decades has established that atherosclerosis is a chronic inflammatory disorder. Among the potentially critical sources of vascular inflammation during atherosclerosis are the components of pathogenic bacteria, especially lipopolysaccharide (LPS). Toll-like receptor (TLR)-4, expressed on different inflammatory cells involved with the recognition of bacterial LPS, has been recognized to have mutations that are prevalent in a number of ethnic groups. Such mutations have been associated with a decreased risk of atherosclerosis. In addition, epidemiological investigations have proposed that LPS confers a risk factor for the development of atherosclerosis. Gram-negative bacteria are the major source of LPS in an individual's serum, which may be generated during subclinical infections. The major cell receptors on inflammatory cells involved in the pathogenesis of atherosclerosis, like macrophages, monocytes, and dendritic cells (DCs), are CD14, MD-2, and LPS binding protein (LBP). These receptors have been blamed for the development of atherosclerosis through dysregulated activation following LPS recognition. Lipoproteins may also play a role in modulating the LPS-induced inflammatory events during atherosclerosis development. In this review article, we attempt to clarify the role of LPS in the initiation and progression of atherosclerotic lesion development.
几十年来，越来越多的科学证据表明，动脉粥样硬化是一种慢性炎症性疾病。在动脉粥样硬化过程中，潜在的血管炎症的关键来源之一是致病细菌的成分，尤其是脂多糖（LPS）。Toll 样受体（TLR）-4 在识别细菌 LPS 方面，在不同的炎症细胞中表达，已经被发现存在于许多种族中普遍存在的突变。这种突变与动脉粥样硬化风险降低有关。此外，流行病学研究表明 LPS 赋予了动脉粥样硬化发展的危险因素。革兰氏阴性菌是个体血清中 LPS 的主要来源，它可能在亚临床感染期间产生。在动脉粥样硬化发病机制中涉及的炎症细胞（如巨噬细胞、单核细胞和树突状细胞）上的主要细胞受体是 CD14、MD-2 和 LPS 结合蛋白（LBP）。这些受体通过 LPS 识别后失调激活，被指责导致动脉粥样硬化的发展。脂蛋白也可能在调节动脉粥样硬化发展过程中 LPS 诱导的炎症事件中发挥作用。在这篇综述文章中，我们试图阐明 LPS 在动脉粥样硬化病变发展中的起始和进展中的作用。
