Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux

Abstract

The residual risk for arteriosclerotic cardiovascular disease after optimal statin treatment may amount to 50% and is the consequence of both immunological and lipid disturbances. Regarding the lipid disturbances, the role of triglyceride-rich lipoproteins (TRLs) and their remnants has come to the forefront in the past decade. Triglycerides (TGs) stand as markers of the remnants of the catabolism of TRLs that tend to contain twice as much cholesterol as compared to LDL. The accumulation of circulating TRLs and their partially lipolyzed derivatives, known as “remnants”, is caused mainly by ineffective triglyceride catabolism. These cholesterol-enriched remnant particles are hypothesized to contribute to atherogenesis. The aim of the present narrative review is to briefly summarize the main pathways of TRL metabolism, bringing to the forefront the newly discovered role of apolipoproteins, the key physiological function of lipoprotein lipase and its main regulators, the importance of the fluxes of these particles in the post-prandial period, their catabolic rates and the role of apo CIII and angiopoietin-like proteins in the partition of TRLs during the fast-fed cycle. Finally, we provide a succinct summary of the new and old therapeutic armamentarium and the outcomes of key current trials with a final outlook on the different methodological approaches to measuring TRL remnants, still in search of the gold standard.

Lipid Profile and Cardiovascular Risk Modification after Hepatitis C Virus Eradication

“…Alternatively, they are again hydrolyzed by hepatic lipase, whereby IDLs are transformed into LDLs, depleted of TGs and high in cholesterol. These particles transport cholesterol to peripheral tissues or the liver via APOB100 interactions with LDL receptors [ 23 ].…”

“…Notably, most of the patients who developed cardiovascular disease after HCV treatment had no obvious risk factors prior to antiviral therapy [ 23 , 98 ].…”

The chylomicron saga: time to focus on postprandial metabolism

“…Actually, they float in plasma left overnight in the refrigerator, a classical and simple test to determine their presence. Of note, all liposoluble vitamins in the diet are also carried by chylomicrons ( 8 , 31 – 33 ).…”

“…In essence, the hypothesis states that atherogenesis is mediated in part by cholesterol-rich remnant particles stemming from chylomicrons (CM) and very-low density lipoproteins (VLDL). In spite of the fact that we spend much of the day in the fed state ( 1 , 5 – 7 ), analytical difficulties have delayed the progress of a thorough and comprehensive study of postprandial lipid metabolism and determined that most diagnostic and treatment goals only take into account the fasting lipoprotein and lipid levels ( 8 – 11 ).Since statins have had such remarkable therapeutic success over the past three decades, the field has become somewhat LDL-centric and has dismissed the importance of triglycerides (TG) and particularly chylomicrons in atherogenesis ( 8 , 12 – 14 ). Nonetheless, numerous individuals using statins still run the risk of developing atherosclerotic cardiovascular disease (ASCVD) and are unable to achieve their target LDL-C levels ( 15 – 19 ).…”

“…This residual risk, which may reach 50% after receiving effective statin therapy, results from both immunological and lipid abnormalities. The significance of triglyceride rich lipoproteins (TRL) and their remnants in these key lipid abnormalities has gained attention in recent years ( 8 , 16 , 20 ). Ineffective intravascular TG metabolism and recapture lead to the accumulation of circulating TRL and their “remnants” or partially lipolyzed derivatives.…”