Which lipoprotein is associated with cholesterol build up in the arteries

HDL-C plays a key role in the reverse transportation of cholesterol by accepting cholesterol from lipid-laden macrophages Lehrke et al. In the study conducted by Khera et al. It was also discovered that the associations persisted after adjustment for traditional cardiovascular risk factors, including the levels of HDL cholesterol and apolipoprotein A-I. In addition to being carrier proteins for the HDL particle, these proteins have protective roles which they play against cardiovascular diseases, such as by acting as anti-inflammatory regulators to limit the activity of pro-inflammatory cytokines.

Nascent HDL is synthesised and secreted by the liver and small intestine. It travels in the circulation where it gathers cholesterol to form mature HDL, which then returns the cholesterol to the liver via various pathways. This protein increases the efflux of cholesterol from tissue to liver where it is excreted. It has low measured HDL-C levels yet very low rates of cardiovascular events even with high blood cholesterol values Franceschini et al.

Phospholipids are transferred from macrophages by a specific transporter molecule known as ATP-binding cassette transport protein A1 ABCA-1 into the core of the lipoprotein, and cholesterols are extracted from the cells by a transporter protein derived from macrophages in the sub-endothelial spaces of tissues; ABCG-1 transporter.

The eventual maturation of the HDL particle is dependent on the lecithin: cholesterol acyltransferase LCAT , an enzyme activated by apoAI, which catalyses the formation of cholesterol esters from cholesterol. Endocytosis of the matured HDL into hepatocytes occurs and the cholesterol and cholesterol esters are transported via a facilitated transfer to distinct pools within the cell. The modified HDL particles are secreted back into circulation where they can further acquire cholesterol before they re-circulate to the liver.

The complete reverse cholesterol transport occurs with the addition of apo E to the HDL particle which facilitates their uptake and catabolism. Activation of lipoprotein lipase LpL activity has been reported to have anti-atherogenic activity. Lipoprotein lipase LpL is a rate-limiting enzyme found on the surface of endothelial cells. It is polypeptide with amino acids and an extracellular domain which binds to apo B and apo E.

The enzyme digests the TAG to fatty acids and monoglycerides. This provides non-esterified fatty acids and 2-monoacylglycerol which can be utilised immediately by cells for energy production or synthesis of other lipids.

Unutilized fatty acids may be bound to circulating albumin and released slowly to meet future cellular requirements. Glycerol produced from LpL activity is transported back to the liver and kidneys, where it is converted to dihydroxyacetone phosphate in the alternative glycolytic pathway.

The fatty acids from LpL activity in the muscle may diffuse into cells to be oxidized to two-carbon units or used to re-synthesis TAG which are stored in adipose cells Clee et al. Significant LpL activity occurs in muscle, adipose tissue and lactating mammary glands. Both carrier proteins are necessary for recognition of IDL and LDL by the LDL receptors in the liver, after which they are taken up into hepatocytes by endocytosis and catabolized.

Research carried out over the past two decades have not only established a central role for LpL in the overall lipid metabolism and transport but have also identified additional, non-catalytic functions of the enzyme. Furthermore, abnormalities in LpL function have been found to be associated with a number of pathophysiological conditions, including atherosclerosis, chylomicronaemia, obesity, Alzheimer's disease, and dyslipidaemia associated with diabetes, insulin resistance, and infection Mead et al.

LpL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. Severe mutations that cause LpL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LpL are linked to many disorders of lipoprotein metabolism. LpL isozymes are regulated differently depending on the tissue. For example, insulin is known to activate LpL in adipocytes and its placement in the capillary endothelium. By contrast, insulin has been shown to decrease expression of muscle LpL Kiens et al.

The form that is in adipocytes is activated by insulin, whereas that in muscle and myocardium is activated by glucagon and epinepherine. This helps to explain why during fasting, LpL activity increases in muscle tissue and decreases in adipose tissue.

After feasting, the opposite occurs Braun and Severson, ; Mead et al. The concentration of LpL displayed on endothelial cell surface cannot be regulated by endothelial cells, as they neither synthesize nor degrade LpL. Instead, this regulation occurs by managing the flux of LpL arriving at the lipolytic site and being released into circulation attached to lipoproteins Braun and Severson, ; Goldberg, The typical concentration of LpL in plasma is in the nanomolar range.

Lipoprotein lipase deficiency leads to hypertriglyceridemia elevated levels of triglycerides in the bloodstream and decreased high density lipoprotein activity Clee et al. Diets high in refined carbohydrates have been shown to cause tissue-specific overexpression of LpL.

Several studies have reported conflicting reports on the effect of hormonal replacement therapy on plasma LDL-C and Lp a levels Taskinen et al.

In a cohort study conducted by Danik et al. It was reported that the relationship of high Lp a levels with increased cardiovascular disease is modified by hormonal therapy. These data suggest that the predictive utility of Lp a is markedly attenuated among women taking HT and may inform clinicians' interpretation of Lp a values in such patients. It was noteworthy that the effect of hormonal therapy was observed only in women with high LDL cholesterol levels, in agreement with previous studies suggesting an interaction between Lp a and LDL cholesterol Berglung and Anuurad, Small, dense lipoprotein sub-fractions have been reported to have atherogenic potentials, with particular reference to Lipoprotein a [Lp a ], a variant of low density lipoprotein LDL.

These sub-fractions are characterized by the presence of apolipoprotein B, with an additional apolipoprotein known as apo a in the Lp a structure. Apo a is structurally and functionally similar to plasminogen and it accounts for virtually all the genetic variability in plasma Lp a levels. Variation of length within the kringle 4-encoding region of the apo a gene may account for a greater proportion of the inter-individual variation in plasma Lp a concentrations, with a strong genetic involvement inherited as a single autosomal dominant trait.

In the course of the pathogenesis of atherosclerosis, oxidized LDL is taken up by macrophages and into endothelial cells. This leads to formation of atherosclerotic plaques which precedes development of CHD. Such risk factors were identified as hypertriglyceridemia, reduced HDL-C levels, abdominal obesity and insulin resistance.

Treatment of CHD can be achieved by lowering of plasma cholesterol levels which has been achieved by cholesterol-lowering therapy, suggesting that maintenance of low cholesterol levels may sufficiently prevent or reverse an established atherosclerosis. Increasing plasma levels of HDL-C has been reported to also be of benefit.

HDL-C has anti-inflammatory activity which may prevent oxidation of LDL and it plays a key role in reverse transportation of cholesterol from lipid-laden macrophages. Activation of the enzyme is dependent on the tissue, resulting in variability of its activity.

Hormonal replacement therapy may also be of benefit to patients with CHD and related diseases, but reported on current findings are conflicting. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.

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What are lipids? Table 1. Physical properties and lipid compositions of lipoprotein classes. Role of cholesterol in membrane dynamics It is relevant to establish the important of cholesterol in the body to be able to relate the various metabolic events associated with cholesterol and its homeostasis.

Lipoproteins, cholesterol and atherosclerosis Cholesterol is a building block of the outer layer of cell membranes. Atherogenicity of lipoprotein sub-fractions The first stages of cholesterol build up in the blood vessels atherosclerosis occur when LDL particles circulating in the blood penetrate through the inner lining of blood vessels and become trapped in the artery wall.

Apolipoproteins in lipoproteins Apolipoproteins are the carrier proteins for lipoproteins and they consist of a single polypeptide chain often with relatively little tertiary structure.

Main structural protein. Table 2. Classes of apolipoproteins, their molecular weight and functions. Apolipoprotein E Three isoforms of this apolipoprotein exist and they are all synthesised mainly by the liver and also by several tissues such as arterial wall, brain and adipose tissue.

Apolipoprotein C Apolipoprotein C is subdivided into three and each has its own distinct function. Transfer of apolipoproteins in lipoprotein homeostasis Lipids enter blood circulation bound to apolipoproteins as chylomicrons or VLDL which as secreted into the blood stream from the intestines.

Apolipoprotein a Apolipoprotein a itself is a large glycoprotein that exhibits size heterogeneity among individuals with isoforms that range between — kDa in size. Synthesis of lipoprotein a Apo a is expressed by liver cells hepatocytes , and the assembly of apo a and LDL particles seems to take place at the outer hepatocyte surface.

Similarity between lipoprotein a and plasminogen The structure of Lp a is similar to plasminogen, a naturally occurring glycoprotein that participates in dissolving of clots that form in the bloodstream, and tissue plasminogen activator tPA. Correlation between apolipoprotein size and Lp a concentration There is a general inverse correlation between the size of the apo a isoform and the Lp a plasma concentration Bowden et al.

Role of oxidation in atherogenesis Oxidative stress, especially LDL oxidation has been suggested for almost three decades as the most probable aetiology of atherosclerosis Steinbrecher et al. Relationship between insulin resistance, diabetes, and small, dense LDL Cardiovascular heart disease risk is usually significantly increased when elevated levels of small, dense LDL accompanied by hypertriglyceridemia, reduced HDL-cholesterol levels, abdominal obesity, and insulin resistance.

Dyslipoproteinaemia Dyslipoproteinaemia is a term broadly used for derangement in lipid and lipoprotein metabolism, which may either be hyperlipoproteinaemia or hypolipoproteinaemia. Theories of atherogenesis Arteries are blood vessels that carry oxygenated blood from the heart to all tissues of the body. This process is called atherosclerosis.

Skip directly to site content Skip directly to page options Skip directly to A-Z link. Section Navigation. Facebook Twitter LinkedIn Syndicate. If a clot or blockage forms in a narrowed artery to the heart or the brain, a heart attack or stroke can result. About one-fourth to one-third of blood cholesterol is carried by HDL. HDL cholesterol is known as "good" cholesterol, because high levels of HDL seem to protect against heart attack. HDL tends to carry cholesterol away from the arteries and back to the liver, where it's passed from the body — in a way, it "eats" up the bad cholesterol.

Some experts believe that HDL removes excess cholesterol from arterial plaque, slowing its buildup. Triglyceride is a form of fat made in the body. This combination of proteins and cholesterol is called a lipoprotein.

There are different types of cholesterol, based on what the lipoprotein carries. They are:. A lipid profile also typically measures triglycerides, a type of fat in the blood. Having a high triglyceride level also can increase your risk of heart disease. Factors you can control — such as inactivity, obesity and an unhealthy diet — contribute to harmful cholesterol and triglyceride levels. Factors beyond your control might play a role, too. For example, your genetic makeup might make it more difficult for your body to remove LDL cholesterol from your blood or break it down in the liver.

Cholesterol levels can also be worsened by some types of medications you may be taking for other health problems, such as:. If you have too many cholesterol particles in your blood, cholesterol may accumulate on your artery walls.

Eventually, deposits called plaques may form. The deposits may narrow — or block — your arteries. These plaques can also burst, causing a blood clot to form. High cholesterol can cause a dangerous accumulation of cholesterol and other deposits on the walls of your arteries atherosclerosis. These deposits plaques can reduce blood flow through your arteries, which can cause complications, such as:. The same heart-healthy lifestyle changes that can lower your cholesterol can help prevent you from having high cholesterol in the first place.

To help prevent high cholesterol, you can:. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version.