High-density lipoprotein and endothelial function in patients with myocardial infarction: Pieces in a puzzle

Like the colorful lights of the aurora borealis, high-density lipoproteins (HDLs) are full of character and inspire wonder. Their extremely heterogeneous polymolecular complexity and multidimensional functionality demands careful scrutiny, or else their wondrous nuances could go unappreciated [1–3]. Indeed, while epidemiological observations have suggested an important role of HDL in protection from cardiovascular disease (CVD), recent clinical trials have tempered enthusiasm over simply raising the quantity of cholesterol within HDL [4–7]. The lack of positive clinical trials in this space has only increased motivation for a deeper understanding of how pieces of the puzzle fit together in the HDL-CVD relationship. Over the life course of an HDL particle, there is continual remodeling of the lipidome and proteome, and these dynamic structural changes appear to dictate functionality. Reverse cholesterol transport is the classic function, but not necessarily the most important one. Other described HDL functions include platelet reactivity, heme metabolism, vitamin binding, insulin secretion, immunity, and as addressed in this issue by Carvalho et al. [7]– antioxidative/anti-inflammatory activity and regulation of endothelial function. Translational mechanistic studies like Carvalho et al.'s are important to bridging the spac