Dysfunctional High-Density Lipoprotein Cholesterol and Coronary Artery Disease: A Narrative Review

作者：Cristina Madaudo, Giada Bono, Antonella Ortello, Giuseppe Astuti, Giulia Mingoia, Alfredo Ruggero Galassi, Vincenzo Sucato · 发表于：Journal of Personalized Medicine · 年份：2024 · DOI：10.3390/jpm14090996 · 被引用次数：51 · 研究领域：Lipoproteins and Cardiovascular Health、Diabetes, Cardiovascular Risks, and Lipoproteins、Cancer, Lipids, and Metabolism

High-density lipoprotein (HDL) cholesterol is traditionally viewed as protective against cardiovascular disease (CVD). However, emerging evidence reveals that dysfunctional HDL, characterized by impaired reverse cholesterol transport (RCT), reduced anti-inflammatory and antioxidant activities and increased endothelial dysfunction, which can contribute to coronary artery disease (CAD). Dysfunctional HDL, resulting from oxidative modifications of Apolipoprotein A-1 (Apo A-1) and enzyme inactivation, fails to effectively remove cholesterol from peripheral tissues and may promote inflammation and atherosclerosis. Genetic mutations affecting HDL metabolism further complicate its role in cardiovascular health. Studies have shown that conventional therapies aimed at raising HDL-C levels do not necessarily reduce cardiovascular events, highlighting the need for new approaches that improve HDL functionality. Therapeutic strategies such as Apo A-1 mimetic peptides, reconstituted HDL infusions, and drugs targeting specific HDL metabolic pathways are being explored. Additionally, weight loss, statin therapy, and niacin have shown potential in enhancing HDL function. The pathophysiology of dysfunctional HDL involves complex mechanisms, including oxidative stress, inflammation, and genetic mutations, which alter its structure and function, diminishing its cardioprotective effects. New functional assays, such as the cholesterol efflux capacity (CEC) and HDL inflammatory index, provide more ...