HDL3-C subfractions are significantly and inversely associated with arterial stiffness, suggesting that HDL subfractions are likely more important than HDL-C in preventing cardiovascular disease.
Broadly, HDL can be distinguished into two subfractions, by density: HDL2 cholesterol (HDL2-C) and HDL3 cholesterol (HDL3-C). HDL3-C is well approximated by the sum of small and medium HDL particles (HDL-P), whereas HDL2-C correlates strongly with large HDL-P. There is no consensus, however, on the functions of HDL2-C and HDL3-C. Whereas some researchers have confirmed that large HDL-Ps have a protective effect on CHD, others recognized that the small, dense, protein-rich HDL-Ps display more potent atheroprotective properties than large, buoyant cholesterol-rich particles.
HDL3 carries enzymes that prevent oxidative stress and receives cholesterol from reverse cholesterol transport through the ATP-binding cassette transporter A1 mediators. Earlier studies that measured the cholesterol content of HDL subclasses using density gradient ultracentrifugation suggested that the large HDL2-C subfractions are better predictors of CHD. With the availability of newer HDL measures, however, more recent studies using the same separation technique have found that smaller HDL3-C subfractions play this role.
References:
Wang, F., Wang, X., Ye, P. et al. High-density lipoprotein 3 cholesterol is a predictive factor for arterial stiffness: a community-based 4.8-year prospective study. Lipids Health Dis 17, 5 (2018). https://doi.org/10.1186/s12944-017-0650-z
Salonen JT, Salonen R, Seppänen K, Rauramaa R, Tuomilehto J. HDL, HDL2, and HDL3 subfractions, and the risk of acute myocardial infarction. A prospective population study in eastern Finnish men. Circulation. 1991 Jul;84(1):129-39. doi: 10.1161/01.cir.84.1.129. PMID: 2060089.
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