Low-density Lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. LDL is often referred to as "bad cholesterol" due to its association with an increased risk of atherosclerosis and cardiovascular diseases. LDL particles are the primary carriers of cholesterol in the blood and play a significant role in the lipid metabolism.

Overview

LDL particles are composed of a core of esterified cholesterol and triglycerides, surrounded by a shell of phospholipids and free cholesterol, and contain one molecule of apolipoprotein B-100 (ApoB-100) on their surface. ApoB-100 serves as a recognition signal for cellular receptors to capture and internalize the particle.

Function

The main function of LDL is to deliver cholesterol to cells, where it is used in membranes, or for the synthesis of steroid hormones and bile acids. However, high levels of LDL cholesterol in the blood can lead to the deposition of cholesterol on artery walls, forming plaques that narrow the arteries and increase the risk of heart attack, stroke, and peripheral artery disease.

Pathophysiology

When LDL particles invade the endothelium and become oxidized by the cells of the immune system, they can trigger an inflammatory response. Macrophages engulf the oxidized LDL, forming foam cells and fatty streaks in the arterial walls, which are early signs of atherosclerosis.

Measurement and Classification

LDL cholesterol is typically measured by calculating the amount in the blood. The Friedewald formula is commonly used, which estimates LDL cholesterol as total cholesterol minus HDL cholesterol minus triglycerides divided by five. However, this method has limitations, especially when triglyceride levels are high or very low.

LDL particles vary in size and density, and smaller, denser LDL particles are thought to be more atherogenic than larger, less dense particles. Techniques such as nuclear magnetic resonance spectroscopy and gradient gel electrophoresis can differentiate between these particles, providing more detailed information about cardiovascular risk.

Management

Management of high LDL cholesterol involves lifestyle changes such as diet, exercise, and weight loss, along with pharmacotherapy if necessary. Statins are the most commonly prescribed drugs for lowering LDL cholesterol. They work by inhibiting the enzyme HMG-CoA reductase, which is crucial for cholesterol synthesis in the liver. Other medications include ezetimibe, which reduces intestinal cholesterol absorption, and PCSK9 inhibitors, which increase the removal of LDL from the blood.

Prevention

Preventive measures against high LDL cholesterol include maintaining a healthy diet rich in fruits, vegetables, whole grains, and lean proteins, while limiting intake of saturated fats, trans fats, and cholesterol. Regular physical activity and avoiding tobacco smoke are also important in maintaining healthy cholesterol levels.

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