Cholesterol in arteries

Atherosclerosis is a wide-spread pathology, manifested chiefly by the deposition of cholesterol in arterial walls, which results in the formation of lipid plaques (atheromas). Lipid plaques are specific foreign bodies around which the connective tissue develops abnormally (this process is called sclerosis). This leads to the cal-cification of the impaired site of a blood vessel. The blood vessels become inelastic and compact, the blood supply through the vessels is impeded, and the plaques may develop into thrombi. 

In the B-100,E receptor-deficient WHHL rabbit, LDL is taken up by a low-affinity mechanism whose net activity increases as the concentration of LDL increases (i.e., the pathway is not subject to feedback control from intracellular cholesterol). In normal rabbits the B-100,E receptor is calculated to account for 63, 92, and 83% of LDL degraded by the liver, adrenal gland, and intestine, respectively (P18). Whether the low-affinity mechanism alone is responsible for the localized accumulations of cholesterol in artery walls or tendons, seen in human familial hypercholesterolemia and also in the WHHL rabbit, is uncertain perhaps local trauma, or some other additional factor is also required. 

Cholesterol (below, see also Section 23.4B) Is an alcohol that Is a precursor of steroid hormones and a vital constituent of cell membranes. It Is essential to life. On the other hand, deposition of cholesterol In arteries is a cause of heart disease and atherosclerosis, two leading causes of death in humans. For an organism to remain healthy, there has to be a delicate balance between the biosynthesis of cholesterol and its utilization, so that arterial deposition is kept at a minimum. 

In the field of lipids the only studies made until relatively quite recently were on frozen tissue sections, which ranged in thickness from 5 to 10 p. These were used in combination with emulsions in the form of stripping film which reduces the contrast of the preparation and makes more accurate localization quite difficult. Better resolution was sought by reducing the thickness of the section and application of liquid emulsion, and some improvement was obtained in the study of cholesterol localization in aorta (Charman and Lipsky, 1967). Another approach was the use of Carbowax, a water miscible wax, which allows the preparation of relatively thin sections (about 4 p). This method of tissue preparation was utilized for the study of phosphatidylinositol metabolism in the pancreas (Hokin and Hueb-ner, 1967) and of the distribution of cholesterol- in arteries and other tissues (Kramsch et al., 1967). The suitability of the Carbowax embedding for the study of lipids has been based on its being miscible with water and on the feasibility of performing lipid stains on sections prepared from Carbowax-embedded tissue. 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

Familial hypercholesterolemia is characterized by a selective elevation in plasma LDL and deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas). 

The goals of treatment are to lower total and LDL cholesterol in order to reduce the risk of first or recurrent events such as myocardial infarction, angina, heart failure, ischemic stroke, or other forms of peripheral arterial disease such as carotid stenosis or abdominal aortic aneurysm. 

Increased cholesterol levels in serum are found in patients suffering from chronic hepatitis, atherosclerosis (deposit of fat in arteries of heart) and hypothyroidism,... 

There is a mutant gene that produces an inactive receptor and patients with this mntant snffer from high levels of LDL-cholesterol in their blood. They have a markedly increased risk of developing atherosclerosis and coronary artery disease. 

Even during the first or second decade of life, small deposits of lipid, fatty streaks, are often detectable in arterial walls. In a study by R. Ross over half of the children (age 10-14) examined at autopsy had fatty streaks in their arteries. These are the first indications of the entry of fat and cholesterol into macrophages in the subendothelial space of an artery. This initiates a sequence of processes that eventually produces a plaque. A prerequisite for the development of fatty streaks, and hence atherosclerosis, is injury to the endothelial cells fining the arterial wall. Many factors are suspected of causing this, including pollutants. 

One role of high density lipoprotein (HDL) is to collect unesterified cholesterol from cells, including endothelial cells of the artery walls, and return it to the liver where it can not only inhibit cholesterol synthesis but also provide the precursor for bile acid formation. The process is known as reverse cholesterol transfer and its overall effect is to lower the amount of cholesterol in cells and in the blood. Even an excessive intracellular level of cholesterol can be lowered by this reverse transfer process (Figure 22.10). Unfortunately, the level of HDL in the subendothelial space of the arteries is very low, so that this safety valve is not available and all the cholesterol in this space is taken up by the macrophage to form cholesteryl ester. This is then locked within the macrophage (i.e. not available to HDL) and causes damage and then death of the cells, as described above. 

Atherosclerosis is a condition of the organism characterized by elevated levels of atherogenic lipoproteins in blood plasma, lipid deposits (including cholesterol) in the form of esters inside walls of the arterial system, and it is expressed by a gradual difficulty of blood circulation. The most appropriate name for this disease is lipoproteinemia. Clinically, it is manifested in the form of ischemic heart disease, stroke, abnormal cerebral blood flow, and peripheral ischemia. 

POOH Anderson]. W., S. Riddell-Mason, N. J. Gustafson, S. F. Smith, and M. Mackey. Cholesterol-lowering effects of psyllium-enriched cereal as an adjunct to a prudent diet in the treatment of mild to moderate hypercholesterolemia. Amer J Clin Nutr 1992 56(1) 93-98. Day, C. E. Activity of psyllium hydrophilic colloid for reducing serum cholesterol in sea quail fed diet supplemented with cholesterol. Artery 1991 18(3) 163-167. 

Was this your answer Unsaturated fats are not so readily used by your body to synthesize cholesterol. They also tend to increase the proportion of high-density lipoproteins, which lower the level of cholesterol in your blood and help relieve the buildup of arterial plaque. 

Although elevated levels of cholesterol and LDL in human plasma are linked to an increased incidence of cardiovascular disease, recent data have shown that an increase in concentration of HDL in plasma is correlated with a lowered risk of coronary artery disease. Why does an elevated HDL level in plasma appear to protect against cardiovascular disease, whereas an elevated LDL level seems to cause this disease The answer to this question is not known. An explanation currently favored is that HDL functions in the removal of cholesterol from nonhepatic tissues and the return of cholesterol to the liver, where it is metabolized and secreted. The net effect would be a decrease in the amount of plasma cholesterol available for deposit in arteries (see... 

High levels of plasma cholesterol do not directly cause heart attacks. Rather, over long periods cholesterol is somehow involved in the progressive development of a disease of the arteries called atherosclerosis. Atherosclerotic plaques are complex lesions in arterial walls that contain abnormal deposits of cholesteryl esters. Precisely how high cholesterol levels in the plasma relate to the development of atherosclerosis is not understood and is a major frontier of medi-... 

It is a diuretic. An extract of the flowers and leaves improves cardiac output and the contractility of the heart muscle. Flavonoids in hawthorn have been shown to increase blood flow in the heart by dilating blood vessels in coronary arteries. Hawthorn has lowered cholesterol in animal studies, probably due to its oligomeric procyanidins (OPC), a type of bioflavonoid similar to that found in the extracts of grape seed and grape skin. 

In summary, the consumption of garlic appears to reduce serum cholesterol in experimental animals in a dose-dependent fashion. This may be due to decreased synthesis or increased excretion of cholesterol through the intestinal tract. It has been reported that garlic consumption increases high-density lipoprotein (HDL) levels, which may help to remove excess cholesterol from arterial tissue. 

Third, acyl-CoA cholesterol acyltransferase (ACAT) [EC 2.3.1.26], an enzyme that works after the formation of cholesterol, was considered a unique target of inhibition [32], ACAT catalyzes the synthesis of cholesteiyl esters from cholesterol and long-chain fatty acyl-CoA. ACAT plays important roles in the body, for example, in the absorption of dietary cholesterol from the intestines, production of lipoprotein in liver and formation of foam cells from macrophages in arterial walls. Therefore, ACAT inhibition is expected not only to lower plasma cholesterol levels but also to have a direct effect at the arterial wall. A number of synthetic ACAT inhibitors such as ureas, imidazoles, and acyl amides have been developed [33], Several groups have searched for novel ACAT inhibitors... 

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