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Pathophysiology of acute coronary syndrome
Published in K Sarat Chandra, AJ Swamy, Acute Coronary Syndromes, 2020
JPS Sawhney, Prashant Wankhade, Simran Sawhney
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.
PAI-1 Activity and Serum Lipid Levels
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Endothelial cell surfaces are covered with complex carbohydrates, such as glycosaminoglycans. These glycosaminoglycans act as receptors for lipoproteins, mediating their passage into the cell interior. Interactions of glycosaminoglycans on the arterial wall with circulating low-density lipoproteins (LDL) are important in the pathogenesis of atherosclerosis; complexes of the two are often found in atherosclerotic lesions.6,7 An elevated level of LDL is >4.5 mmol/1. Accumulation of LDL after endothelial cell injury may promote chondroitin sulfate excretion by proliferating smooth muscle cells. LDL bound to cell receptors is then available for complex formation with glycosaminoglycans in the arterial wall.8 Foam cell formation is enhanced by LDL uptake in the macrophages. After oxidative or enzymatic degradation, which inhibits the interaction with lipoprotein receptors on the arterial wall, LDL is taken up by receptors on the macrophages.9
Fat
Published in Geoffrey P. Webb, 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.
Papain exerts an anti-atherosclerosis effect with suppressed MPA-mediated foam cell formation by regulating the MAPK and PI3K/Akt-NF-κB pathways
Published in Expert Opinion on Therapeutic Targets, 2023
Xianming Fei, Lianlian Pan, Wufen Yuan, Yan Zhao, Lei Jiang, Qinghua Huang, Yan Wu, Guoqing Ru
We evaluated the number of foam cells in each group using Oil Red O staining. As shown in Figure 3a, compared with the control group, many red lipid droplets appeared in the cells of the model group, which conformed to the morphological characteristics of foam cells and indicated that the number of foam cells had increased. Compared with the model group, the number of lipid droplets in the papain and BAY11-7082 groups was decreased. However, after treatment with TNF-α and papain, the number of lipid droplets increased significantly. In addition, we evaluated the intracellular triglyceride, MCP-1, and PGE2 levels in each group (Figure 3b-c). The results showed that the levels of triglycerides, MCP-1, and PGE2 in cells increased significantly after modeling, and the application of papain and BAY11-7082 effectively inhibited the expression of triglycerides, MCP-1, and PGE2 (Figure 3b-c, P < 0.05). However, TNF-α treatment reversed the inhibitory effect of papain on these indices (Figure 3b-c, P < 0.05).
Hypolipemic effects of histamine is due to inhibition of VLDL secretion from the liver: involvement of both H1 and H2-receptors
Published in Archives of Physiology and Biochemistry, 2022
The change of vascular permeability is the second mechanism whereby histamine affects plasma lipids. The vascular endothelium is a semipermeable barrier that ultra-filtrates the plasma and regulates the solute composition of interstitial fluids. The flux of particles from plasma into the layer of intima depends on its plasma concentration, the size of particles, and permeability of the interface at the endothelium-intima layer (Rasouli and Kiasari 2008). At the level of any tissue, LDL is transferred from the bloodstream to the cells membrane (cholesterol influx) and returned back to the plasma for excretion (cholesterol efflux), the latter process is known as cholesterol revers transport. It is reported that secretion of histamine by mast cells within the intima layer increases locally vascular permeability for LDL and HDL. This effect is mediated via H1-receptors and stimulates the formation of atherosclerotic lesions (Rasouli and Kiasari 2008, Rozenberg et al.2010). The imbalance between cholesterol influx and efflux causes accumulation of excess cholesterol in macrophages that now have been converted to foam cells. Thus, we propose that in the presence of histamine or its agonists, plasma LDL will be directed to the atherogenic pathway leading to decrease plasma lipids.
Understanding the role of alternative macrophage phenotypes in human atherosclerosis
Published in Expert Review of Cardiovascular Therapy, 2022
Kenji Kawai, Aimee E. Vozenilek, Rika Kawakami, Yu Sato, Saikat Kumar B Ghosh, Renu Virmani, Aloke V. Finn
Fernandez examined single cell RNA-seq data from human carotid plaque from subjects with clinically significant disease [recent stroke or transient ischemic attack (TIA)] and compared them to asymptomatic disease (no stoke or TIA) subjects [146]. Five distinct clusters of macrophages were identified with significantly different functional heterogeneity. Clusters 1, 2, and 3 were more activated and proinflammatory than Cluster 5, which was consistent with a more foam cell signature. In subjects with asymptomatic disease, macrophages were more activated, pro-inflammatory, and displayed enhanced foam cell function compared to macrophages from symptomatic subjects. Subjects with symptomatic plaques demonstrated macrophage subsets demonstrating PPARα and/RXRα signaling know to drive M2 polarization, as described above. Another cluster was characterized by enrichment for genes responsible for iron metabolism and storage representing alternatively activated macrophages involved in the clearance of iron derived from hemoglobin. Combined with data from mice including lineage tracing models, single cell analyses are beginning to enhance our understanding of different macrophage subtypes in human atherosclerosis.