Cholesterol in tissues

The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins (apolipoproteins or apoproteins). The lipoprotein particles include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They differ in lipid and protein composition, size, and density (Figure 18.13). Lipoproteins function both to keep their component lipids soluble as they transport them in the plasma, and also to provide an efficient mechanism for transporting their lipid contents to (and from) the tissues. In humans, the transport system is less perfect than in other animals and, as a result, humans experience a yradual deposition of lipid—especially cholesterol—in tissues. This is a potentially life-threat-en ng occurrence when the lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). 

Katsanidis, E. and Addis, P.B. 1999. Novel HPLC Analysis of Tocopherols, Tocotrienols, and Cholesterol in Tissue. Free Radic. Biol. Med. 27 1137-1140. 

The effectiveness of pectin in lowering cholesterol in tissues can be influenced by many factors (1) The type of pectin - that with methoxy groups and with high viscosity (35, 36) was reported to be more effective. The results from a comparative study of several types of pectin by Mokady (36) are shown in Table IV. Neither a high degree of methylation nor high-viscosity alone was very effective (2) the level of dietary fat - with a high-fat diet (2% corn oil plus 18% beef tallow), pectin has no effect on serum cholesterol level (57). Tsai et al. also reported that with... 

The main transport form of lipids in the cir culation. They are spherical macromolecules of 10-1200 nm diameter-composed of a core of neutral lipids (mostly cholesterol ester and triglycerides) surrounded by an amphipathic shell of polar phospholipids and cholesterol. Embedded in the shell of lipoproteins are apolipoproteins that are essential for assembly of theparticles in tissues that secrete lipoproteins, and for their recognition by target cells. 

MANY FACTORS INFLUENCE THE CHOLESTEROL BALANCE IN TISSUES... 

In tissues, cholesterol balance is regulated as follows (Figure 26-5) Cell cholesterol increase is due to uptake of cholesterol-containing Hpoproteins by receptors, eg, the LDL receptor or the scavenger receptor uptake of free cholesterol from cholesterol-rich hpoproteins to the cell... 

Most commonly, the lipid metabolism pathology is manifest as hyperlipemia (elevated concentration of lipids in blood) and tissue lipidoses (excessive lipid de-position in tissues). Normally, the lipid contents in the blood plasma are total lipids, 4-8 g/litre triglycerides, 0.5-2.1 mmol/litre total phospholipids, 2.0-3.5 mmol/litre total cholesterol, 4.0-8.0 mmol/litre (esterified cholesterol accounts for 2/3 of total cholesterol). 

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. 

Niacin reduces plasma LDL cholesterol, lipoprotein (a), triglycerides and raises HDL cholesterol in all types of hyperlipoproteinemia [26]. Although available on the market for more than 40 years, the mechanisms of action of niacin are poorly understood. Putative mechanisms are the activation of adipose tissue LPL, diminished HTGL activity, a reduced hepatic production and release of VLDL, and composi-... 

Sutherland KM, Brady H, Gayo-Fung LM, Leisten J, Lipps SG, McKie JA, et al. (2003) Effects of SP500263, a novel selective estrogen receptor modulator, on bone, uterus, and serum cholesterol in the ovariectomized rat. Calcif Tissue Int 72 710-716... 

Details of plasma lipoproteins and their metabolism are given in Section 5.5. Most of the cholesterol in the blood is carried as part of low density lipoprotein (LDL) or high density lipoprotein (HDL), whereas most triglyceride, in the fasting state, is carried by very low density lipoprotein (VLDL). The relative concentrations of these lipoproteins constitute the lipid profile and determine CVD risk. Diabetics are more likely to show an unhealthy profile with elevated concentrations of LDL and triglyceride but reduced HDL concentration. This pattern can be partly explained by enhanced fatty acid liberation from adipocytes as a consequence of insulin resistance in that tissue and due to reduced removal from the circulation of triglycerides, which is also insulin dependent. 

A high plasma concentration of LDL (usually measured as LDL-cholesterol) is a risk factor for the development of atheroma whereas a high concentration of HDL is an anti-risk factor for cardiovascular disease (CVD). Fundamental discoveries relating to cholesterol metabolism and the importance of the LDL receptor made by Nobel laureates Joseph Goldstein and Michael Brown led to an understanding of the role of LDL in atherosclerosis. The impact of HDL in reducing CVD risk is often explained by the removal of excess cholesterol from tissues and its return to the liver, a process known as reverse cholesterol transport. However, evidence from research by Gillian Cockerill and others shows that HDL has a fundamental anti-inflammatory role to play in cardioprotection. 

In addition to extracellular degradation in tissues, endosomal acidification might also trigger PEG-lipid cleavage. We showed that despite the presence of the PEG, which slightly reduces lipoplex internalization into the cells, DNA transfection level almost reaches the level of the cationic lipo-plex (31). Cholesterol PEG incorporation into lipoplexes not only reduces lipoplex internalization, but also inhibits the transfection efficiency. 

Although both LDL and HDL are primarily cholesterol particles, most of the cholesterol measured in the blood is assodated with LDL. The normal role of LDL is to deliver cholesterol to tissues for biosynthesis. When a cell is repairing membrane or dividing, the cholesterol is required for membrane synthesis. Bile acids and salts are made from cholesterol in the liver, and many other tissues require some cholesterol for steroid synthesis. As shown in Figure 1-15-6, about 80% of LDL are picked up by hepatocytes, the remainder by peripheral tissues. ApoB-100 is the only apoprotein on LDL, and endocytosis of LDL is mediated by apoB-100 receptors (LDL receptors) clustered in areas of cell membranes lined with the protdn clathrin. 

HDL particles are able to transfer cholesterol from tissue cells to LDL particles. In this way, cholesterol is transported from tissues to the liver. 

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