Special proteins, apoproteins, play an important role in moving lipoproteins around the body and facilitating their interactions with other cells. The most important of these are the apoB class, residing on VLDL, IDL, and LDL particles, and the apoA-I class, residing for the most part on the HDL particles.
VLDL are one of the major triglyceride-rich lipoproteins. They carry endogenous, hepatically synthesized triglycerides, largely derived from dietary carbohydrate or from plasma NEFA (=Non-Esterified Fatty Acids), and are of a large size (30–60 nm diameter).
Each VLDL particle has a single molecule of a larger apoB form, apoB100, with other apolipoproteins (apoE and apoCs) being acquired in plasma from HDL.
The levels of VLDL are not the only thing that matters. The size and chemical makeup of VLDL particles also contribute to health risks.
VLDL size is dependent on the triglyceride content, with large buoyant triglyceride-enriched VLDL being formed at times of triglyceride excess.
These large VLDL may be a poorer substrate for the usual path of metabolism involving apoCII-dependent activation of LPL and apoCII-LPL binding similar to that seen with chylomicrons, and thus have a longer residency time in the blood. As triglyceride is hydrolyzed, VLDL particles shrink with loss of surface components to HDL and subsequent catabolism to LDL via IDL. This process is less efficient in the presence of high triglyceride levels and large buoyant VLDL. A longer plasma residency time allows a greater exchange of triglyceride from VLDL into LDL and HDL with reverse exchange of cholesterol ester, mediated by cholesterol ester transfer protein (CETP). This produces cholesterol-enriched VLDL remnants that are less readily metabolized to LDL and can be removed by alternative, but potentially atherogenic, pathways. Additionally, this process produces triglyceride-enriched LDL that shrink as some triglyceride is hydrolyzed in the liver by another endothelial enzyme, hepatic lipase, producing small, dense LDL.
References:
J.P.D. Reckless, J.M. Lawrence, HYPERLIPIDEMIA (HYPERLIPIDAEMIA), Editor(s): Benjamin Caballero, Encyclopedia of Food Sciences and Nutrition (Second Edition), Academic Press, 2003, Pages 3183-3192, ISBN 9780122270550, https://doi.org/10.1016/B0-12-227055-X/00613-1. (https://www.sciencedirect.com/science/article/pii/B012227055X006131)
Lucero D, Zago V, López GH, Cacciagiú L, López GI, Wikinski R, Nakajima K, Schreier L. Predominance of large VLDL particles in metabolic syndrome, detected by size exclusion liquid chromatography. Clin Biochem. 2012 Mar;45(4-5):293-7. doi: 10.1016/j.clinbiochem.2011.12.013. Epub 2012 Jan 3. PMID: 22245548.
McEneny J, McPherson P, Spence M, Bradley U, Blair S, McKinley M, Young I, Hunter S. Does a diet high or low in fat influence the oxidation potential of VLDL, LDL and HDL subfractions? Nutr Metab Cardiovasc Dis. 2013 Jul;23(7):612-8. doi: 10.1016/j.numecd.2011.12.007. Epub 2012 Mar 8. PMID: 22405535.
Sacks FM. The crucial roles of apolipoproteins E and C-III in apoB lipoprotein metabolism in normolipidemia and hypertriglyceridemia. Curr Opin Lipidol. 2015 Feb;26(1):56-63. doi: 10.1097/MOL.0000000000000146. PMID: 25551803; PMCID: PMC4371603.
Notø AT, Mathiesen EB, Brox J, Björkegren J, Hansen JB. The ApoC-I content of VLDL particles is associated with plaque size in persons with carotid atherosclerosis. Lipids. 2008 Jul;43(7):673-9. doi: 10.1007/s11745-008-3193-2. Epub 2008 May 29. PMID: 18509687.
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Metabolic syndrome is associated with large VLDL [L]. Metabolic syndrome is the medical term for a combination of diabetes, high blood pressure (hypertension) and obesity. It puts you at greater risk of getting coronary heart disease, stroke and other conditions that affect the blood vessels.
The key aspect is to collaborate with your doctor to identify the underlying cause of your elevated VLDL-C levels and address any associated conditions. Depending on your medical history and test results, your doctor may prescribe cholesterol-lowering medication [L].
To effectively lower your VLDL cholesterol, it is crucial to focus on reducing your triglyceride levels. This can be achieved by implementing healthy lifestyle modifications, such as losing excess weight and engaging in regular exercise. Additionally, it is advised to limit the consumption of sugary foods and alcohol, as these substances have a significant impact on triglyceride levels [L].
By following these lifestyle adjustments and working closely with your doctor, you can effectively manage and lower your VLDL cholesterol levels, mitigating the associated risks of heart disease and other related conditions [L].
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