Cholesterol

Cholesterol was first described near the end of the 18th century by a French chemist, Antoine Francois de Fourcroy, and then named ‘cholesteroline’ by Michel Eugene Chevreul in 1815. Cholesterol is an insoluble constituent of animal fats found among the lipids in the bloodstream and in all cells of the human body. As an essential component of cell membranes and serum lipoproteins, cholesterol enables transmembrane transport and the transport of triglycerides. As a precursor of bile acids, cholesterol aids in the absorption of fat in the intestine. And as a precursor to adrenal steroids and sex hormones, cholesterol aids in endocrine regulation. When regulated properly by the body, cholesterol ensures survival. When regulated improperly, cholesterol threatens good health. Elevated serum cholesterol levels often lead to the buildup of arterial plaques, heart attack, and even death.

Cholesterol originates in one of two ways: either in the bile or through the diet. The intake of biliary cholesterol is typically 600 to 1,000 mg per day, while the intake of dietary cholesterol is only 250 to 500 mg per day. Biliary cholesterol is primarily synthesized from acetyl CoA through the HMG-CoA reductase pathway in many cells and tissues.

Since it is insoluble, cholesterol cannot travel freely through the blood. Cholesterol transport in the body is achieved through the use of lipoproteins. Lipoproteins consist of a core of neutral lipids surrounded by a polar surface coat that allows for the transport of cholesterol and other insoluble triglycerides. There are five major classes of lipoproteins: chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). LDL carry triglycerides and cholesterol on to other body cells, while HDL transport cholesterol back to the liver for excretion.

Of the lipoprotein fractions, LDL, IDL, and VLDL are considered atherogenic. Conversely, increased concentrations of HDL correlate with lower rates of atherosclerosis. LDL pass through the arterial walls and become modified to form fatty streaks that in turn become fibrous plaques and finally lesions. These lesions often bring about calcification, hemorrhage, and ulceration. Atherosclerosis usually remains asymptomatic until an atheroma obstructs the bloodstream in the artery, and angina or myocardial infarction may subsequently develop.

Physiological and behavioral risk factors for atherosclerosis and coronary heart disease include age, heredity, diabetes, obesity, high blood pressure, and smoking, among others. In 1986, the statins, a class of pharmaceuticals that disrupt cholesterol biosynthesis by inhibiting HMG-CoA reductase, first became commercially available. Since then, the statins have emerged as the most effective therapeutic regimen for controlling a patient's blood cholesterol level, and clinical trials have repeatedly confirmed that altering lipoprotein transport significantly lowers a patient's risk for and incidence of cardiovascular disease.