Large LDL and small HDL particles: The best combination

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Nelson Vergel

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Large LDL and small HDL particles: The best combination

High-density lipoprotein (HDL) is one of the five main types of lipoproteins found in circulation, together with very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and chylomicrons.

After a fatty meal, the blood is filled with chylomicrons, which carry triglycerides (TGAs). The TGAs are transferred to cells from chylomicrons via the activity of enzymes, in the form of free fatty acids (FFAs), which are used by those cells as sources of energy.

Large LDL and small HDL particles: The best combination

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Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice.

 
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he study has just been published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. The researchers recruited 180 healthy participants with an average age of nearly 77 and analyzed samples of their blood plasma and cerebrospinal fluid. Using a sensitive technique known as ion mobility, originally developed by study co-author Ronald Krauss, M.D., at the University of California, San Francisco, the investigators were able to identify, count and measure the size of individual HDL particles. A subset of 141 participants also completed a battery of cognitive tests.

Of the participants who took the cognitive tests, the ones with higher levels of small HDL particles in their cerebrospinal fluid performed better, independent of their age, sex, education or whether or not they carried the APOE4 gene, which puts them at higher risk for Alzheimer’s disease. The correlation was even stronger among those who had no cognitive impairment. The evidence suggests that these HDL particles may be key to finding treatments that would work early in the disease process, long before cognitive decline occurs.

“What we’re finding here is that before the onset of cognitive impairment, these oils — these small HDL particles — are lubricating the system and keeping it healthy,” he said. “You’ve got a time to intervene with exercise, drugs or whatever else to keep brain cells healthy. We still need to understand the mechanisms that promote the production of these particles, in order to make drugs that increase small HDL in the brain.”

 
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