The Atherogenic Action of Triglycerides
The elevated plasma triglyceride levels can be:
• Genetically determined (primary hypertriglyceridemia)
• Secondary causes (Metabolic syndrome, diabetes mellitus, obesity, etc)
• Adverse drug reactions
• Postprandial hypertriglyceridemia
The increased plasma triglyceride levels are mainly caused by high chylomicron levels and hepatic derived Very Low Density Lipoproteins levels (VLDL).
Chylomicrons are formed by enterocytes and they are complexes that transfer food triglycerides – and to a lesser degree cholesterol - from the gut to the peripheral cells.
In normal conditions, chylomicrons, VLDL and VLDL remnants are rapidly metabolized and removed from the circulation via specific receptors and are not converted into small dense complexes which are atherogenic.
*Nordestgaard BG, Freiberg JJ.Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol.CurrVascPharmacol. 2011 May; 9 (3):281-6
Regarding postprandial hypertriglyceridemia (WHERE THE FAT TOLERANCE TEST IS POSITIVE) the following changes take place:
Small dense LDL are more atherogenic than LDL due to:
1. Easier penetration to the arterial wall
2. Endothelial cell toxicity
3. Promotion of synthesis of Plasminogen activator inhibitor-1 (PAI-I) and the Thromboxane by endothelial cells
4. Easier oxidation
5. Easier adhesion to glycosaminoglycans of the arterial wall
6. Less connection with macrophage scavenger receptors than with the LDL receptor
*Nordestgaard BG, Freiberg JJ.Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol.CurrVasc Pharmacol. 2011 May; 9(3):281-6.
These small dense LDL initially are not connected to LDL specific receptor (which is their initial destination), but they are withdrawn from the circulation by other receptors known as scavenger receptors which are found in macrophages.
Prolonged elevated postprandial plasma triglyceride levels promote atherosclerosis
in the following ways:
1. Formation of the more atherogenic small dense LDL by loading LDL with triglycerides.
2. Formation of small dense HDL which are not as functional as normal HDL, by loading HDL with triglycerides.
3. Increase of plasma triglycerides remnants, which have atherogenic action as well.
Fasting and non-fasting triglyceride determination cannot establish the diagnosis of postprandial hypertriglyceridemia. So it is recommended to measure postprandial triglyceride levels.