HDL and LDL

 

HDL and LDL are the transport carriers of cholesterol between the liver and the rest of the body.

They are best known for their role atherosclerosis.

Target levels in the blood are:

 

High Density Lipoproteins


HDLs are secreted directly into the blood from the liver and intestine, and are important for various functions.

They serve as a reservoir of apo C-II and apo E for transfer to other lipoproteins. Nascent HDLs are disc shaped, but due to their high concentration of phospholipid they rapidly accumulate unesterified cholesterol from other lipoproteins or cell membranes.

This makes them candidate molecules to mop up cholesterol from developing or existing atheromas on vessel walls.

 

HDL cholesterol is esterified by the enzyme PCAT, and transported to VLDLs. HDLs also transport cholesterol to the liver for disposal or to steroidogenic cells, forming a key component of cholesterol homeostasis. There is thus an inverse relationship between [HDL] and atherosclerosis as it mediates reverse cholesterol transport.

 

Exercise and moderate alcohol consumption raise HDL levels, while obesity and smoking lower them.

 

 

Low Density Lipoproteins

 

A healthy LDL is between 2-4 mmol/L. Target numbers change based on risk factors.

The higher the LDL, the higher the risk of cardiovascular problems (Ballantyne, 1998).

 

The primary function of LDLs is to deliver cholesterol to tissues. They have much less TAGs, but more cholesterol, than VLDLs. They are normally taken up (endocytosed) by cells across the body. However, when LDL levels are too high (hypercholesterolemia), LDL gets deposited in blood vessel walls.

 

 

LDL and Atherosclerosis

Macrophages can endocytose oxidized LDL using scavenger receptors class A (SR-A). Accumulation of cholesterol esters converts macrophages into foam cells, which are important mediators of atherosclerosis


 

Normal LDL Uptake

They do through recognition of apo B-100 or apo E (but not apo B-48) by LDL receptors. These receptors are glycoproteins that are associated with clathrin-coated pits. Following endocytosis, the vesicle fuses with endosomes, the receptors are recycled, and lipid contents are used by the cell. Following endocytosis, LDL receptor expression is downregulated. Excess cholesterol is esterified for storage by acyl CoA:cholesterol acyltransferase (ACAT).

Mutations in the LDL receptor, or in apo B-100, lead to type II hyperlipidemia.

Thyroid hormone, T3, facilitates LDL binding with its receptor. As such, hypothyroidism is a common cause of hyperlipidemia.

 


Resources and References

 

Ballantyne CM. Am J Cardiol 1998;82:3Q-12Q

 

Can J Cardiol 2006;22:913-26