When was cholesterol discovered

When studying cholesterol characteristics in the population, there is some indication of an inverse relationship between HDL levels and cardiovascular risk. In other words, it seems like high HDL is correlated with low heart attack numbers. From a mechanistic standpoint, this makes sense. In the body, HDL acts to remove cholesterol from specialized cells called macrophages , which helps to prevent the build-up of cholesterol in our blood vessels.

Furthermore, it has been proposed that HDL has antioxidant and anti-inflammatory properties, which are beneficial when it comes to heart disease. In some contexts, HDL can become damaged, transforming into something that actually promotes damage to our blood vessels. Thus, HDL levels may not be an informative parameter at the individual level. The idea that raising HDL might be beneficial came from clinical studies, including the coronary Drug Trial , where the effects of niacin were examined.

Interestingly, niacin also lowers LDL-cholesterol, as well as another type of blood lipid called triglycerides. Because of this, it is hard to tease out whether the protective effects of niacin are actually related to raising HDL levels. Fibrates , such as TriCor or Lopid , are another class of compounds that can significantly raise HDL levels, but, like niacin, these drugs also affect LDL and triglycerides.

Despite some of the uncertainties, several pharmaceutical companies were driven to explore potential cardio-protective effects of specifically raising HDL levels in the blood stream.

Based largely on the work of Alan Tall at the Columbia University Medical Center, many pharmaceutical labs are working on targeting a molecule in our body called cholesteryl ester transfer protein , more easily referred to as CETP. Studies have shown that blocking the action of CETP leads to an increase in HDL levels in the blood, and, based on the notion that increased HDL is beneficial, it is thought that these drugs would be a great option to what we already have on the market.

However, the first drug trial investigating a CETP-inhibitor had disastrous consequences. The hope was that this biochemical data would translate into a heart-protective effect in humans. These results occurred because torcetrapib was reported to increase blood pressure. And it is this reasoning that the idea of CETP inhibition has not been totally abandoned. In a Phase III study, it was reported that anacetrapib had significant HDL-raising effects when administered to patients already taking a statin, and this was without any of the off-target effects seen with torcetrapib.

In May of this year, the NHLBI announced that they would be prematurely halting this clinical study, which was investigating the effects of taking niacin on top of a statin, citing futility. This decision was made after taking into consideration the negative results from the ACCORD lipid study , which showed that taking a fibrate in combination with a statin provided no extra benefit for diabetic patients. Given the currently available data, LDL appears to be the major risk factor when it comes to cardiovascular disease susceptibility.

Should we re-interpret the early studies showing an association between high HDL and a lower incidence of heart attacks? As the investigation into the efficacy of anacetrapib moves forward, perhaps we will become more informed. But what is the point if it is only being tested on top of a statin? However, there are always ethical considerations to take into account. It is not good practice to prevent a patient from taking a medication that is known to be beneficial to their condition, just so we can make a point in the name of science.

This is certainly quite relevant when speaking about the percentage of the population who just cannot tolerate statin therapy because of unwanted side effects. There has got to be a way to ensure that everyone has an equal chance at fighting heart disease and perhaps it is time to restructure our current approach.

For many high-risk patients who do not respond to diet and exercise, getting their LDL levels in check is as simple as taking a statin. Statins are drugs that inhibit the natural ability of our body to generate cholesterol and result in the reduction of LDL cholesterol in the blood. These medications have certainly helped many, especially those who are genetically predisposed to high cholesterol levels due to heredity.

The particles transporting cholesterol circulating in the blood are LDL. LDL, the major cholesterol carrier in the blood, is a spherical particle Figure 1. Its core consists of some 1, cholesteryl esters, each a cholesterol molecule attached by an ester linkage to a long fatty acid chain. The oily core is shielded from the aqueous plasma by a coat composed of unesterified cholesterol, phospholipid and one large protein molecule, apoprotein B. A normal healthy person has approximately 2 g cholesterol per liter plasma.

The highest abnormal values, approximately 10 g per liter, are found in persons with a severe disease called familial hypercholesterolemia FH , which is an inborn error of metabolism. Figure 1. The LDL is a spherical particle with a radius of one millionth millimeter.

Most of the cholesterol in the blood stream is found in LDL particles. Its core consists of approximately 1, cholesteryl esters, each a cholesterol molecule attached by an ester linkage to a long fatty acid chain. The core is surrounded by a surface coat composed of molecules of phospholipid, molecules of unesterified cholesterol and one large protein molecule, apoprotein B, which moors the LDL to the receptor on the cell surface.

Cholesterol has two main functions in the body. It constitutes a structural component in cell membranes, and it is converted to certain steroid hormones and bile salts.

More than 90 per cent of the cholesterol in the body is found in cell membranes. Each cell is surrounded by a membrane, the cell or plasma membrane.

Its function is not only to be a protective coat. It also serves as a border control determining which substances are allowed to enter or leave the cell. This function is sometimes facilitated by the presence of specific receptors whereby certain molecules are efficiently trapped and taken up by the cell.

The cells either produce their own cholesterol or take up LDL circulating in the blood stream. The discovery of the LDL-receptor by Brown and Goldstein in was a milestone in cholesterol research. Several hormones are produced from cholesterol like estrogen and testosteron, cortison and aldactone. Cholesterol is stored in cells of the adrenals and gonads and can be utilized as soon as there is a requirement for these hormones. Cholesterol also takes part in the synthesis of vitamin D which prevents development of rickets.

Another vital function of cholesterol is associated with food intake. Cholesterol is converted into bile acids in the liver and is transported via the bile to the upper intestine where the bile salts emulsify the dietary fat making it absorbable.

The bile salts then return to the blood stream and are taken up by the liver and again secreted into the upper intestine. As stated above cholesterol is of vital importance for the body. Thus, cholesterol deficiency, a rare disease, causes severe damage particularly in the nervous system. Preparation and properties of serum and plasma proteins XXV.

Pederson K. On a low-density lipoprotein appearing in normal human plasma. Schneider W. Beisiegel O. Purification of the low-density lipoprotein receptor, an acid glycoprotein of , molecular weight. Rittenberg D. Deuterium as an indicator in the study of intermediary metabolism. VI synthesis and destruction of fatty acids in the organism. Chem Tominaga T. Zeit Thannhauser S. Magendantz H. The different clinical groups of xanthomatous diseases: a clinical physiological study of 22 cases.

Utermann G. Hees M. Steinmetz A. Polymorphism of apolipoprotein E and occurrence of dysbeta lipoproteinemia in man. Nature Lond. Virchow R. Wein, Med. Wang X. Sato R. Hua X. SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell 77 53 Oxford University Press is a department of the University of Oxford.

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Sign In or Create an Account. Sign In. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Olson Robert E. Oxford Academic. Cite Cite Robert E. Select Format Select format. Permissions Icon Permissions. Abstract The idea of a fat transport system in the plasma of mammals evolved slowly over three centuries. Table 1 Composition of lipoproteins in blood plasma.

Open in new tab. Open in new tab Download slide. Table 2 Human plasma apolipoproteins. Molecular weight. Plasma level. F LCAT, lecithin:cholesterol acyl transferase.

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