Fat
Geoffrey P. Webb in Nutrition, 2019
When LDL-cholesterol levels in blood rise beyond a certain level then it is taken up by macrophages in the blood vessel walls and circulating monocytes and these LDL-laden macrophages are termed foam cells because they have a foamy appearance. These foam cells accumulate in the blood vessel wall giving rise to so-called fatty streaks which are an early and relatively benign stage in the process of atherosclerosis. At this “fatty streak” stage the process is clearly reversible; some fatty streaks disappear but others undergo hardening and fibrosis and become atherosclerotic plaques. HDL is involved in the process of removal of cholesterol from fatty streaks and plaques and returning it to the liver and high-HDL levels are known to be associated with reduced risk of CHD. It is not really clear why some fatty streaks regress and others develop into plaques but one suggested mechanism is that oxidation of the LDL can make it much more damaging to the artery wall. This theory has also led to suggestions that antioxidants, particularly in fruits and vegetables, may inhibit the progress of atherosclerosis. High-fruit and -vegetable intake is strongly associated with reduced risk of heart disease and reduced total mortality but as discussed in Chapter 13; early suggestions that antioxidant supplements might reduce cancer and cardiovascular disease and prolong life have not been supported by the results of controlled trials and they seem more likely to do net harm than good.
Coronary artery disease
Swati Gupta, Alexandra Marsh, David Dunleavy, Kevin Channer in Cardiology and the Cardiovascular System on the move, 2015
Early lesion: fatty streakEarly precursor of the atherosclerotic plaque.Present from childhood in the aorta, from adolescence in the coronary arteries.Deposition of foam cells in the intima of muscular artery walls: Foam cells are macrophages that migrate into the intima in response to inflammation caused by harmful oxidized low-density lipoprotein (LDL) molecules in the arterial wall.Macrophages ingest lipids through special scavenger receptors.Macrophages may undergo necrosis and rupture, depositing lipids.Not all fatty streaks will progress to become atherosclerotic plaques.
Pathophysiology of acute coronary syndrome
K Sarat Chandra, AJ Swamy in Acute Coronary Syndromes, 2020
There are various stages of plaque maturation as described by the American Heart Association (AHA) [6]. The early stages, i.e. AHA types I–III, are not associated with evidence of structural damage to the endothelium. The fully developed fibro-lipid plaque, designated as type IV or type Va, has a core of lipid surrounded by a capsule of connective tissue. The core consists of an extracellular mass of lipid containing cholesterol and its esters. This core is surrounded by numerous macrophages, many of which are foam cells, i.e. macrophages containing abundant intracytoplasmic droplets of cholesterol. Monocytes which crossed the endothelium from the arterial lumen serve as precursors for these macrophages. These macrophages are highly activated cells and produce a procoagulant tissue factor and various inflammatory cell mediators such as interleukins, tumour necrosis factor-α (TNF α) and metalloproteinases. Smooth muscle cells synthesise collagen which forms the connective tissue capsule surrounding this inflammatory mass. This portion of the capsule separating the core from the arterial lumen forms the plaque cap.
Inclisiran inhibits oxidized low-density lipoprotein-induced foam cell formation in Raw264.7 macrophages via activating the PPARγ pathway
Published in Autoimmunity, 2022
Zhaoping Wang, Xiangyu Chen, Jingxing Liu, Yingcui Wang, Suhua Zhang
Foam cell formation is associated with the regulation of cholesterol influx and efflux. Its steady-state imbalance is closely related to the development of AS [33]. Intracellular cholesterol levels are dynamically regulated by scavenger receptors and reverse cholesterol transporter [34]. Certain scavenger receptors participate in cellular lipid uptake, notably SR-A, LOX-1, and CD36 [35,36]. [Gly14]-humanin reduces the expression of CD36 and LOX-1 to reduce the internalization of ox-LDL, thus inhibiting foam cell formation [37]. Ginkgo biloba extract downregulated SR-A expression to ameliorate foam cell formation in macrophages [38]. Consistently, our data revealed that inclisiran significantly reduced the protein levels of CD36, SR-A, and LOX-1 in the macrophages in a concentration-dependent manner. SR-BI, ApoE, and ABCA1 are key proteins in reverse cholesterol transporters that promote macrophage cholesterol efflux and prevent foam cell formation [39,40]. Sage weed (Salvia plebeia) extract has a significant inhibitory effect on the expression of SR-BI, ABCA1, and ABCG1 induced by ox-LDL, thereby preventing the formation of foam cells derived from macrophages [41]. In this study, SR-BI, ABCA1, and ApoE were significantly upregulated by inclisiran, indicating that inclisiran can promote cholesterol efflux.
Lipogenic stromal cells as members of the foam-cell population in human atherosclerosis: Immunocytochemical and ultrastructural assessment of 6 cases
Published in Ultrastructural Pathology, 2022
Yong-Xin Ru, Zhang Xue-Bin, Xiao-Ling Yan, Dong Shu-Xu, Zhang Yongqiang, Li Ying, Liu Jing, Brian Eyden
Any hypothesizing on the origin of the lipid-bearing foam cells in atherosclerosis must be based on a secure knowledge on the phenotypic characterization of the foam-cell population. The name “foam cell” is a morphological descriptor based simply on the presence of foamy cytoplasm, the latter widely regarded as consisting of lipid (rather than membrane-bound vacuoles). In the present study of carotid atherosclerotic plaques (CAPs), we aim to show that the histological term “foam cell” encompasses at least four phenotypically distinct cells, each with separate differentiations, which can be identified on the basis of histological, immunocytochemical and ultrastructural criteria. We also discuss the value of CD68, widely regarded as a macrophage marker, in the evaluation of these subpopulations.
A study on the transport and interaction between blood flow and low-density-lipoprotein in near-wall regions of blood vessels
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2021
Satyajit Choudhury, Kameswararao Anupindi, B. S. V. Patnaik
Today cardiovascular diseases are the leading cause of death globally (WHO 2017) and atherosclerosis is the root of most of these diseases. Atherosclerosis initiates with the accumulation of atherogenic lipoproteins and their aggregates in the intima of an arterial wall (Lusis 2000; Chandran et al. 2012). Its initiation is characterised by the development of cholesterol engorged macrophages known as foam cells at some preferential sites in the arteries that are dictated by blood flow dynamics. Though the foam cells or fatty streaks are not very relevant clinically, these, after a series of complex bio-chemical reactions can lead to the formation of advanced stage lesions resulting in stenosed arteries, or even worse, in the formation of thrombus due to rupture of the necrotic core of the lesion (Lusis 2000). Another pathological condition is an abdominal aortic aneurysm (AAA) which is a condition where the aortic segment just upstream of the iliac bifurcation expands irreversibly. Although, the role played by atherosclerotic plaques in the initiation and progression of the disease is not well understood, there are studies that suggest a strong correlation between high levels of low density lipoprotein (LDL) cholesterol and AAA (Harrison et al. 2018; Weng et al. 2018). Often patients with AAA were found to have atherosclerotic plaques. However, it is not clear whether this association between AAA and atherosclerosis is causal or simply due to other common risk factors (Golledge and Norman 2010).
Related Knowledge Centers
- Ester
- Myocardial Infarction
- Smooth Muscle
- Atheroma
- Stroke
- Atherosclerosis
- Monocyte
- Cholesterol
- Macrophage
- Low-Density Lipoprotein