Chapman - Figure 20 - Perspectives Text

So what do we see as the perspectives in this field, and how might new knowledge of the lipidome and the proteome of HDL be relevant to these new perspectives? There are 3 possible major new perspectives.

• The first one is that high throughput diagnostic methodologies should be developed to identify potentially functional anomalies, ie, qualitative anomalies, in the lipidome and/or the proteome of HDL particle subpopulations, in individuals at high risk. Clearly, those qualitative anomalies in the lipidome and/or the proteome must be linked to functional defects in HDL. In other words, we must bring together the lipidome, the proteome, and their functions in order to understand how HDL expresses its atheroprotective activities.
• Second, once the first is understood, then the next new perspective is that we may be able to monitor proteins and lipids in HDL particles in such a way as to provide us with very informative biomarkers of HDL function, and equally, such markers may shed light on the global CVD risk of a given individual. In other words, we believe that biomarkers derived from the HDL proteome and/or lipidome may provide substantially greater information to the clinician compared to a simple measure of plasma HDL cholesterol or apoA-I quantity.
• The third and final perspective is particularly exciting. We believe that in the future, the efficacies of new therapies targeted to correct perturbed HDL metabolism in atherogenic dyslipidemia and cardiometabolic disease should normalize HDL quantity and functionality, and we believe that such therapeutic normalization may be able to be monitored through analyses of the lipidome and/or proteome of HDL particles.

Clearly the new technologies for analysis of HDL particles, in conjunction with our new and evolving functional understanding of the components of HDL particles, can provide insight into new ways to monitor the efficacy of new therapies, and we really believe that monitoring the lipidomic and/or proteomic components of HDL will enable us in the future to evaluate the efficacy of the multiple new therapies that are presently progressing to normalize HDL structure, metabolism, and function in individuals at high CVD risk.

Chapman J. J Clin Lipidol. 2011; 5(6).