2021/07/23 by Manuela Casula, Ornella Colpani, Sining Xie +2 · 2 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Diabetes, Cardiovascular Risks, and Lipoproteins #Lipoproteins and Cardiovascular Health #Cancer, Lipids, and Metabolism
paper · pdf · doi:10.3390/cells10081869
openalex publication_date 2021/07/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
For a long time, high-density lipoprotein cholesterol (HDL-C) has been regarded as a cardiovascular disease (CVD) protective factor. Recently, several epidemiological studies, while confirming low plasma levels of HDL-C as an established predictive biomarker for atherosclerotic CVD, indicated that not only people at the lowest levels but also those with high HDL-C levels are at increased risk of cardiovascular (CV) mortality. This "U-shaped" association has further fueled the discussion on the pathophysiological role of HDL in CVD. In fact, genetic studies, Mendelian randomization approaches, and clinical trials have challenged the notion of HDL-C levels being causally linked to CVD protection, independent of the cholesterol content in low-density lipoproteins (LDL-C). These findings have prompted a reconsideration of the biological functions of HDL that can be summarized with the word "HDL functionality", a term that embraces the many reported biological activities beyond the so-called reverse cholesterol transport, to explain this lack of correlation between HDL levels and CVD. All these aspects are summarized and critically discussed in this review, in an attempt to provide a background scenario for the "HDL story", a lipoprotein still in search of a role.