Evidence that postprandial hyperTG is atherogenic

Mechanisms for how TRL induce CVD. Atherogenesis is initiated by subendothelial retention of lipoproteins[184] and [185]. Large VLDL and CM are too large to enter the arterial wall, but smaller remnants and LDL penetrate the arterial intima and bind to artery wall proteoglycans. This explains why patients who are homozygous for rare deleterious mutations in the LPL gene, causing chylomicronemia with extremely high levels of large chylomicrons and VLDLs, have an increased risk of pancreatitis, but not an increased risk of CVD [100]. Remnants may also be involved in the development of CVD by other pathways than by accumulation of cholesterol in the arterial wall. For example, by inducing endothelial dysfunction, such as impaired vasodilation and enhanced inflammatory response (see review [186]). The accumulation of TRLs generates cholesterol-ester enriched small dense HDL and LDL. The HDL is removed from the circulation leading to low HDL cholesterol. The cholesterol-enriched LDL display increased binding affinity to artery wall proteoglycans [187].

http://www.sciencedirect.com/science/article/pii/S0009898114000321

"In the postprandial state, TRLs comprise CMs synthesized in the intestine, VLDL particles produced in the liver and their cholesterol-rich remnants. Postprandial hypertriglyceridemia can be initiated by both overproduction and/or defective catabolism of TRLs and is caused by both genetic variations and non-genetic factors such as obesity or T2D. Remnants can accumulate in the arterial wall and will deliver more cholesterol than LDL particles. Recent data strongly indicate that both non-fasting triglycerides and remnant cholesterol are not only CHD risk factors but are causally linked to atherogenesis. To date, no randomized clinical trials have addressed the effects of TRL-lowering measures on CVD outcomes, thus hampering recommendations for management. This is partly due to the lack of consensus on clinical measures of biomarkers to screen and assess the postprandial burden of TRLs. Likewise, the failure of clinical intervention trials that aimed to reduce CVD endpoints by lowering plasma TG has raised the urgent need for more extensive clinical endpoint data specifically testing the benefits of lowering postprandial hypertriglyceridemia and remnant cholesterol. However, novel therapy concepts utilizing anti-sense oligonucleotides or siRNA to target regulatory genes of postprandial lipid metabolism provide hope for future management."


http://ac.els-cdn.com/S0021915013006199/1-s2.0-S0021915013006199-main.pdf?

Lipoproteins and the arterial wall.

The figure shows the hypothesis of the mechanism by which remnants and LDL enter and are trapped in the arterial wall, and eventually cause atherosclerosis. HDL = high-density lipoprotein, IDL = intermediate-density lipoprotein, LDL = low-density lipoprotein, VLDL = very-low-density lipoprotein.

http://www.sciencedirect.com/science/article/pii/S016372581300226X

http://www.sciencedirect.com/science/article/pii/S0735109712055210