*Geek Box: Atherogenic Lipoproteins

*Geek Box: Atherogenic Lipoproteins

The size and density of lipoproteins is crucial to understanding the capacity of these compounds to enter into the artery. The following are the major classes of lipoproteins classified according to their size and their density:

  1. Chylomicrons (CM): 75-1,200 nanometers [nm] in diameter
  2. Very-low-density lipoprotein (VLDL): 30-80nm
  3. Intermediate density lipoprotein (IDL): 25-35nm
  4. Low-density lipoprotein (LDL): 18-25nm
  5. High-density lipoprotein (HDL): 5-12nm
  6. Lipoprotein(a) or Lp(a) – technically a sub-type of the LDL class: 25-30nm

‘Density’ refers to the amount of lipid relative to protein (known as ‘apolipoprotein’) of the particle. For example, the composition of VLDL is roughly 92% lipids and 8% protein. Because lipids are large compounds, this means that VLDL are large lipoproteins, but with low-density.

Conversely, the composition of HDL is roughly 58% lipids and 42% protein; this high protein composition makes HDL quite ‘dense’, and the smallest of all lipoprotein subclasses. Thus, more lipid and less protein means a larger, less dense particle. On the other hand, less lipid and more protein means a smaller, more dense particle.

All of these lipoproteins except for HDL are wrapped in apolipoprotein-B, or ApoB. A key feature of ‘forward cholesterol transport’ is the progressive breakdown of triglycerides carried in chylomicrons and VLDL, leading in turn to the formation of chylomicron remnants, IDL, and LDL. With less lipid in the form of triglycerides, these lipoproteins become characterised by their enrichment with cholesterol.

The capacity of cholesterol-enriched lipoproteins to penetrate the arteries is a function of their size. Lipoproteins with a diameter of >75nm are too large to penetrate the artery; thus, chylomicrons and large VLDL particles are not atherogenic (‘atherogenic’ meaning capable of forming fatty deposits in the arteries). The smaller particles, namely: VLDL, IDL, LDL, and Lp(a), are all pro-atherogenic lipoproteins.

Thus, any ApoB-containing lipoprotein of a size <75nm can penetrate the artery and deposit cholesterol. LDL is the primary carrier of cholesterol in circulation, and thus the primary causal lipoprotein in atherosclerosis.