The Chylomicron: Relationship to Atherosclerosis

Abstract

The B-containing lipoproteins are the transporters of cholesterol, and the evidence suggests that the apo B48-containing postprandial chylomicron particles and the triglyceride-rich very low density lipoprotein (VLDL) particles play an important part in the development of the plaque both directly and indirectly by their impact on LDL composition. The ratio of dietary to synthesised cholesterol is variable but tightly regulated: hence intervention with diet at best reduces serum cholesterol by <20% andusually <10%. Statins are the mainstay of cholesterol reduction therapy, but they increase cholesterol absorption, an example of the relationship between synthesis and absorption. Inhibition of cholesterol absorption with Ezetimibe, an inhibitor of Niemann Pick C1-like 1 (NPC1-L1), the major regulator of cholesterol absorption, increases cholesterol synthesis and hence the value of adding an inhibitor of cholesterol absorption to an inhibitor of cholesterol synthesis. Apo B48, the structural protein of the chylomicron particle, is synthesised in abundance so that the release of these particles is dependent on the amount of cholesterol and triglyceride available in the intestine. This paper will discuss cholesterol absorption and synthesis, chylomicron formation, and the effect of postprandial lipoproteins on factors involved in atherosclerosis.

Using primary murine intestinal enteroids to study dietary TAG absorption, lipoprotein synthesis, and the role of apoC-III in the intestine

“…We measured CD36 expression, because it is a major regulator of intestinal lipoprotein secretion, and we found that in the absence of hepatic feedback, CD36 is reduced in hu-apoC-III Tg enteroids. The enteroid culture model presented here, therefore, is not only appropriate for modeling key aspects of dietary fat absorption, but is also potentially critical for determining intestinal mechanisms where lack of hepatic secretions are critical (1,49).…”

“…As the prechylomicron matures, it obtains its apolipoprotein cargo, including apoA-I, apoC-III, and apoA-IV. It is the constellation of these apolipoproteins on the chylomicron that will later direct the metabolism of the particle in the blood and by peripheral tissues such as adipose and liver (1).…”

Chylomicron remnant model emulsions induce intracellular cholesterol accumulation and cell death due to lysosomal destabilization

“…Delayed clearance of chylomicrons is a cause of hypertriglyceridaemia and increases its atherogenicity [14]. Weinstein et al have demonstrated that mice manifesting severe chylomicronemia develop progressive aortic atherosclerosis [15].…”

Roles of triglyceride and phosphate in atherosclerosis of diabetic hemodialysis patients

“…Chylomicron is metabolized and the remaining products of this metabolism play a role in developing of atherosclerosis (37,40). Due to the small size of these remaining products they can simply infiltrate into sub-endothelial space and cause atherosclerotic lesions (41,42).…”