Serum Cholesterol Is Correlated With the Incidence of Atherosclerosis & Coronary Heart Disease

 Atherosclerosis is an inflammatory disease characterized by the deposition of cholesterol and cholesteryl ester from the plasma lipoproteins into the artery wall and is a major cause of heart disease. Elevated plasma cholesterol levels (>5.2 mmol/L) are one of the most important factors in promoting atherosclerosis, but it is now recognized that elevated blood triacylglycerol is also an independent risk factor. Diseases in which there is a prolonged elevation of levels of VLDL, IDL, chylomicron remnants, or LDL in the blood (eg, diabetes mellitus, lipid nephrosis, hypothyroidism, and other conditions of hyperlipidemia) are often accompanied by premature or more severe atherosclerosis. There is also an inverse relationship between HDL (HDL₂) concentrations and coronary heart disease, making the LDL:HDL cholesterol ratio a good predictive parameter. This is consistent with the function of HDL in reverse cholesterol transport. Susceptibility to atherosclerosis varies widely among species, and humans are one of the few in which the disease can be induced by diets high in cholesterol.

Diet Can Play an Important Role in Reducing Serum Cholesterol

 Hereditary factors play the most important role in determining the serum cholesterol concentrations of individuals; however, dietary and environmental factors also play a part, and the most beneficial of these is the substitution in the diet of polyunsaturated and monounsaturated fatty acids for saturated fatty acids. Plant oils such as corn oil and sunflower seed oil contain a high proportion of ω6 polyunsaturated fatty acids, while olive oil contains a high concentration of monounsaturated fatty acids. ω3 fatty acids found in fish oils are also beneficial. On the other hand, butter fat, beef fat, and palm oil contain a high proportion of saturated fatty acids. Sucrose and fructose have a greater effect in raising blood lipids, particularly triacylglycerols, than do other carbohydrates.

One of the mechanisms by which unsaturated fatty acids lower blood cholesterol levels is by the upregulation of LDL receptors on the cell surface, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, ω3 fatty acids have anti-inflammatory and triacylglycerol-lowering effects. Saturated fatty acids also cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic.

Lifestyle Affects the Serum Cholesterol Level

Additional factors considered to play a part in coronary heart disease include high blood pressure, smoking, male gender, obesity (particularly abdominal obesity), lack of exercise, and drinking soft as opposed to hard water. Factors associated with elevation of plasma-free fatty acids (FFAs) followed by increased output of triacylglycerol and cholesterol into the circulation in VLDL include emotional stress and coffee drinking. Premenopausal women appear to be protected against many of these deleterious factors, and this is thought to be related to the beneficial effects of estrogen. There is an association between moderate alcohol consumption and a lower incidence of coronary heart disease. This may be due to elevation of HDL concentrations resulting from increased synthesis of apo A-I and changes in activity of cholesteryl ester transfer protein. It has been claimed that red wine is particularly beneficial, perhaps because of its content of antioxidants. Regular exercise lowers plasma LDL but raises HDL. Triacyl glycerol concentrations are also reduced, due most likely to increased insulin sensitivity, which enhances the expression of lipoprotein lipase.

When Diet Changes Fail, Hypolipidemic Drugs Can Reduce Serum Cholesterol & Triacylglycerol

A family of drugs known as statins have proved highly efficacious in lowering plasma cholesterol and preventing heart disease. Statins act by inhibiting HMG-CoA reductase and upregulating LDL receptor activity. Examples currently in use include atorvastatin, simvastatin, fluvastatin, and pravastatin. Ezetimibe reduces blood cholesterol levels by inhibiting the absorption of cholesterol by the intestine via blockage of uptake by the Niemann-Pick C-like 1 protein. Other drugs used include fibrates such as clofibrate, gemfibrozil, and nicotinic acid, which act mainly to lower plasma triacylglycerols by decreasing the secretion of triacylglycerol and cholesterol containing VLDL by the liver. Since PCSK9 reduces the number of LDL receptors exposed on the cell membrane, it has the effect of raising blood cholesterol levels, thus drugs that inhibit its activity are potentially antiatherogenic and two such compounds, alirocumab and evolocumab, have recently been approved for use and others are currently in development.

Primary Disorders of the Plasma Lipoproteins (Dyslipoproteinemias) Are Inherited

Inherited defects in lipoprotein metabolism lead to the pri mary condition of either hypo- or hyperlipoproteinemia (Table1). For example, familial hypercholesterolemia (FH), causes severe hypercholesterolemia and is associated with premature atherosclerosis. The defect is most often in the gene for the LDL receptor, so that LDL is not cleared from the blood. In addition, diseases such as diabetes mellitus, hypothyroidism, kidney disease (nephrotic syndrome), and atherosclerosis are associated with secondary abnormal lipoprotein patterns that are similar to one or another of the primary inherited conditions. Virtually all of the primary conditions are due to a defect at a stage in lipoprotein formation, trans port, or degradation. Not all of the abnormalities are harmful.

Table1. Primary Disorders of Plasma Lipoproteins (Dyslipoproteinemias)

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مواضيع ذات صلة

Cholesterol is Excreted from The Body in The Bile as Cholesterol or as Bile Acids

Cholesterol is Transported Between Tissue in Plasma Lipoproteins

The Cholesterol Balance in Tissues is Tightly Regulated

Cholesterol Synthesis is Controlled by Regulation of HMG-CoA Reductase

Cholesterol is Biosynthesized From Acetyl-CoA

Brown Adipose Tissue Promotes Thermogenesis

Hormones Regulate Fat Mobilization

Adipose Tissue is The Main Store of Triacylglycerol in The Body

Classification of Proteins

Precipitation Reactions of Proteins

Study of Protein Structure

Imbalance in the Rate of Triacylglycerol Formation & Export Causes Fatty Liver