Dyslipidemia
Jahangir Moini, Matthew Adams, Anthony LoGalbo in Complications of Diabetes Mellitus, 2022
The earliest visible lesion of atherosclerosis is called a fatty streak, a grouping of foam cells filled with lipid within the intimal arterial layer. The fatty streak evolves into the classic atherosclerotic plaque, which contains lipids, inflammatory cells, smooth muscle cells, and a connective tissue matrix (see Figure 8.3). The matrix may have thrombi that are in different stages of organization. Calcium deposits may also be present. All atherosclerotic pathophysiological stages are inflammatory responses to injury, regulated by cytokines. The first causative factor may be endothelial injury. At branch points within the arterial tree, turbulent or nonlaminar blood flow result in endothelial dysfunction. The endothelial production of nitric oxide is inhibited, and vasodilation and anti-inflammatory effects are reduced. The blood flow stimulates endothelial cells, producing adhesion molecules that recruit and then bind inflammatory cells.
Mechanical Effects of Cardiovascular Drugs and Devices
Michel R. Labrosse in Cardiovascular Mechanics, 2018
One of the most prevalent diseases of the cardiovascular system is atherosclerosis, which has been reviewed in Chapter 7. Atherosclerosis is the buildup of cholesterol plaque in the walls of the arteries. The initial lesion usually occurs decades before clinically significant effects are observed; thus, treatment of lesions has evolved as the primary remedy for vessel narrowing due to atherosclerosis. The lesion is marked by intracellular lipid accumulation, forming a fatty streak in the vessel wall. Further lipid accumulation expands to an extracellular lipid pool, which provides a site for calcification. This is followed by increased proliferation of smooth muscle and collagen deposition. When the lesion is severe, it erupts through the vessel wall, attracting platelets and forming a thrombus at the site. Atherosclerosis occurs all over the body but is most problematic in the peripheral, coronary, and cerebral arteries, which feed important capillary beds.
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.
Effects of Egg Consumption and Choline Supplementation on Plasma Choline and Trimethylamine-N-Oxide in a Young Population
Published in Journal of the American College of Nutrition, 2018
Bruno S. Lemos, Isabel Medina-Vera, Olga V. Malysheva, Marie A. Caudill, Maria Luz Fernandez
Cardiovascular disease (CVD) is the leading cause of death worldwide (1). Research targeting the pathogenesis, development, and causes of CVD in various populations is of great interest. Currently, accumulation of fat in the arterial wall can prompt a cascade of events that may result in heart attack, stroke, or death (2). This occurs when low-density lipoprotein (LDL) particles are modified (3) and consequently enter the intima where macrophages engulf them, resulting in foam cell formation (4). The uptake of modified LDL, either oxidized or acetylated, is mainly mediated by scavenger receptors (5) expressed on the surface of macrophages. Eventually, foam cells within the arterial intima will accumulate and form a fatty streak. This will then result in a fibrous cap, at some point rupturing to cause a thrombus (6), which is the main trigger of ischemic events.
Role of protein deimination in cardiovascular diseases: potential new avenues for diagnostic and prognostic biomarkers
Published in Expert Review of Proteomics, 2021
Liqun Mao, Rowann Mostafa, Esra Ibili, Justyna Fert-Bober
Stage II, Formation of lipid layer or fatty streak. The characteristics of stage II are the recruitment of leukocytes and formation of foam cells. The recruited monocytes, neutrophils, and macrophages secrete proinflammatory cytokines (e.g., IL-1β and TNF-α), enzymes (e.g. myeloperoxidase), reactive oxygen species (ROS) that promote further retention and modification of LDLs, as well as many other mediators [120,121]. oxLDLs can activate lesional T cells to secrete proinflammatory cytokines TNF-α, TNF-β, IFN-γ, and IL-2 that can activate macrophages and vascular cells to promote inflammation [113,122]. oxLDLs and cytokines like TNF-α and IL-1β can activate nuclear factor-κB (NF-κB) through canonical NF-κB activation pathways, and the upregulation of NF-κB aggravates chronic inflammation throughout the atherogenesis [120,121]. Notably, PAD4 was shown to citrullinate NF-κB p65 subunit in neutrophils and enhance its interaction with importin-α3 to enter the nucleus and led the expression of proinflammatory mediators, including TNF-α and IL-1β, as confirmed invitro by the inhibition of PAD [123].
Nanotechnological approach to delivering nutraceuticals as promising drug candidates for the treatment of atherosclerosis
Published in Drug Delivery, 2021
Sindhu C. Pillai, Ankita Borah, Eden Mariam Jacob, D. Sakthi Kumar
Reduced shear stress and perturbation in the blood flow at the arteries lead to endothelial cell dysfunction (Deshun & Kassab, 2011). The normal functioning between the smooth muscle cells and the endothelium of arterial vessels is disrupted at the onset of inflammation. Selective solute and cell exchange between the flowing blood and the surrounding tissues is regulated by the vascular endothelium. Small molecules cross the endothelial barrier due to the concentration gradient similarities, whereas the movement of large molecules and cells is permitted only at the impairment of endothelial junctions (Egawa et al., 2013). The pro-atherogenic stimuli and cardiovascular risk factors, such as dyslipidemia, diabetes, obesity, and smoking, cause impairment of endothelial junctions resulting in oxidative stress. Low-density lipoprotein (LDL), one of the most important atherogenic lipoproteins delivers cholesterol (Musunuru & Kathiresan, 2016) to the peripheral tissues (Skålén et al., 2002) which are linked to increased risk of CVD (The Emerging Risk Factors Collaboration, 2009). Endothelial dysfunction allows the entry of LDL into the arterial wall which gets entrapped in the extracellular matrix. Oxidative stress leads to the chemical modification to form oxidative-LDL (Ox-LDL) (Glass & Witztum, 2001), thus activating the endothelium, and up-regulating the vascular cell adhesion molecules (VCAM-1). This is followed by the initial T-cell, monocyte, and leukocyte recruitment (Libby, 2002; Hansson, 2005) which sets the initial stage for atherosclerotic development. Ox-LDL and its oxidized phospholipid components are chemoattractants inducing the expression of monocyte chemotactic protein-1 (MCP-1). MCP-1 attracts monocytes and T-cells that play a fundamental role in the leukocyte recruitment (Falk, 2006) termed as leukocyte extravasation. Monocytes once adhered to the activated endothelial layer, migrate into the intima region differentiating into macrophages with signaling cues received from locally produced monocyte colony-stimulating factor (M-CSF). Macrophage differentiation upregulates scavenger receptor A (SR-A) and CD-36 that mediates the macrophages to assimilate the modified LDL ultimately forming foam cells (Libby, 2002). The yellow discoloration of the arterial wall is the indication of fatty streak formation in atherosclerosis.
Related Knowledge Centers
- Foam Cell
- Tunica Intima
- Endothelium
- Artery
- Atherosclerosis
- Lesion
- Macrophage
- Lipoprotein
- Gross Processing
- Lumen