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Foam cells, also called lipid-laden macrophages, are a type of cell that contain cholesterol. These can form a Atheroma that can lead to atherosclerosis and trigger myocardial infarction and stroke.
Foam cells are fat-laden cells with a Macrophage-like phenotype. They contain low density lipoproteins (LDL) and can be rapidly detected by examining a fatty plaque under a microscope after it is removed from the body. They are named because the lipoproteins give the cell a foamy appearance.
Despite the connection with cardiovascular diseases they might not be inherently dangerous.
Some foam cells are derived from smooth muscle cells and present a limited macrophage-like phenotype.
In response to the inflammatory recruitment signals, are able to penetrate the arterial wall through transendothelial migration, as they can even in healthy arteries. Once in the sub endothelium space, inflammation processes induce the differentiation of monocytes into mature . Macrophages are then able to internalize modified lipoproteins like βVLDL (beta very low density lipoprotein), ACADL (acetylated low density lipoprotein) and OxLDL (oxidized low density lipoprotein) through their binding to the scavenger receptors (SRs) such as CD36 and SR-A on the macrophage surface. These scavenger receptors act as pattern recognition receptors (PRRs) on macrophages and are responsible for recognizing and binding to oxLDL, which in turn promotes the formation of foam cells through internalization of these lipoproteins.
Coated-pit endocytosis, phagocytosis and pinocytosis are also responsible for lipoprotein internalization. Once internalized, scavenged lipoproteins are transported to or for degradation, whereby the cholesteryl esters (CE) are hydrolyzed to unesterified free cholesterol (FC) by Lysosomal lipase (LPL). Free cholesterol is transported to the endoplasmic reticulum where it is re-esterified by ACAT1 (acyl-CoA: cholesterol acyltransferase 1) and subsequently stored as cytoplasmic lipid droplets. These droplets are responsible for the foamy appearance of the macrophage and thus the name of foam cells. At this point, foam cells can either be degraded though the de-esterification and secretion of cholesterol, or can further promote foam cell development and plaque formation – a process that is dependent on the balance of free cholesterol and esterified cholesterol.
The maintenance of foam cells and the subsequent progression of plaque build-up is caused by the secretion of and Cytokinesis from macrophages and foam cells. Foam cells secrete pro-inflammatory cytokines such as interleukins: IL-1, IL-6; tumour necrosis factor (TNF); chemokines: chemokines ligand 2, CCL5, CXC-chemokine ligand 1 (CXCL1); as well as macrophage retention factors. Macrophages within the atherosclerotic legion area have a decreased ability to migrate, which further promotes plaque formation as they are able to secrete cytokines, chemokines, reactive oxygen species (ROS) and growth factors that stimulate modified lipoprotein uptake and vascular smooth muscle cell (VSMC) proliferation. VSMC can also accumulate cholesteryl esters.
In chronic hyperlipidemia, aggregate within the Tunica intima of and become oxidized by the action of oxygen generated either by or endothelial cells. The macrophages engulf oxidized low-density lipoproteins (LDLs) by endocytosis via scavenger receptors, which are distinct from LDL receptors. The oxidized LDL accumulates in the macrophages and other phagocytes, which are then known as foam cells. Kumar, Abbas; Fausto, Aster (2010). "11". Robbins and Cotran: Pathologic Basis of Disease (Eighth Edition International ed.). Philadelphia: Saunders Elsevier. pp. 500–501. . Foam cells form the fatty streaks of the plaques of atheroma in the tunica intima of arteries.
Foam cells are not dangerous as such, but can become a problem when they accumulate at particular foci thus creating a necrotic centre of atherosclerosis. If the fibrous cap that prevents the necrotic centre from spilling into the lumen of a vessel ruptures, a thrombus can form which can lead to Embolus occluding smaller vessels. The occlusion of small vessels results in ischemia, and contributes to stroke and myocardial infarction, two of the leading causes of cardiovascular-related death. However, during the early stages of their pathogenesis, foam cells have also been observed to adopt a pro-fibrotic phenotype in which they increase the stability of a nascent plaque through the up-regulation of the Liver X Receptor (LXR) pathway and the increased expression of extra-cellular matrix (ECM) associated genes.
Foam cells are very small in size and can only be truly detected by examining a fatty plaque under a microscope after it is removed from the body, or more specifically from the heart. Detection usually involves the staining of sections of aortic sinus or artery with Oil Red O (ORO) followed by computer imaging and analysis; or from Nile Red Staining. In addition, fluorescent microscopy or flow cytometry can be used to detect OxLDL uptake when OxLDL has been labeled with 1,1′-dioctadecyl-3,3,3′3′-tetra-methylindocyanide percholorate (DiI-OxLDL).
Autoimmunity occurs when the body starts attacking itself. The link between atherosclerosis and autoimmunity is plasmacytoid dendritic cells (pDCs). PDCs contribute to the early stages of the formation of atherosclerotic lesions in the blood vessels by releasing large quantities of type 1 (INF). Stimulation of pDCs leads to an increase of macrophages present in plaques. However, during later stages of lesion progression, pDCs have been shown to have a protective effect by activating and Treg function; leading to disease suppression.
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