In the latest issue of the Journal of the American College of Cardiology, deGoma et al. reviewed the literature on assessing HDL function on top of plasma HDL cholesterol concentrations. The authors underlined the numerous limitations of plasma HDL cholesterol levels as a surrogate endpoint of HDL function. As reverse cholesterol transport (RCT) appears to account for the bulk of the cardiovascular benefits of HDL particles, the authors suggested a few in vitro and in vivo methodological approaches to estimate RCT in rodents and in humans. The authors highlighted the role of HDL particles as inhibitors of endothelial dysfunction/activation, inflammation/immune activation, and coagulation/platelet activation, along with potential methods to estimate the atheroprotective functions of HDL particles. Moreover, as HDL has been shown to promote endothelial generation of nitric oxide (NO) in vitro, assaying endothelial NO production in response to HDL could provide an in vitro proxy of endothelial function and allow the potentially important effects of HDL to be assessed. In this regard, a method to measure endothelial cell NO generation and vasodilatation was suggested. After reviewing an extensive list of methods that could estimate various aspects of HDL function, the authors concluded that robust, reproducible assays that can be widely performed are needed to advance understanding in the field and enable effective assessment of the therapeutic potential of HDL-targeted therapies.
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