Novel Biomarkers for the Risk Stratification of Heart Failure with Preserved Ejection Fraction.

PURPOSE OF REVIEW: The use of biomarkers in heart failure (HF) is a rapidly changing field. The purpose of this review is to assess the current evidence of the use of biomarkers for risk stratification in patients with HF with preserved ejection fraction (HFpEF). RECENT FINDINGS: Despite differences in pathophysiology between HF with reduced ejection fraction and HFpEF, traditional HF biomarkers such as brain natriuretic peptide and troponin retain prognostic value in most HFpEF-specific populations. Biomarkers of key pathophysiologic components of HFpEF, such as myocardial fibrosis, remodeling, and systemic inflammation are also valuable prognostic markers. Further investigation into HF biomarkers may identify significant therapeutic targets for the treatment of HFpEF.

Saposins modulate human invariant Natural Killer T cells self-reactivity and facilitate lipid exchange with CD1d molecules during antigen presentation.

Lipid transfer proteins, such as molecules of the saposin family, facilitate extraction of lipids from biological membranes for their loading onto CD1d molecules. Although it has been shown that prosaposin-deficient mice fail to positively select invariant natural killer T (iNKT) cells, it remains unclear whether saposins can facilitate loading of endogenous iNKT cell agonists in the periphery during inflammatory responses. In addition, it is unclear whether saposins, in addition to loading, also promote dissociation of lipids bound to CD1d molecules. To address these questions, we used a combination of cellular assays and demonstrated that saposins influence CD1d-restricted presentation to human iNKT cells not only of exogenous lipids but also of endogenous ligands, such as the self-glycosphingolipid ß-glucopyranosylceramide, up-regulated by antigen-presenting cells following bacterial infection. Furthermore, we demonstrated that in human myeloid cells CD1d-loading of endogenous lipids after bacterial infection, but not at steady state, requires trafficking of CD1d molecules through an endo-lysosomal compartment. Finally, using BIAcore assays we demonstrated that lipid-loaded saposin B increases the off-rate of lipids bound to CD1d molecules, providing important insights into the mechanisms by which it acts as a "lipid editor," capable of fine-tuning loading and unloading of CD1d molecules. These results have important implications in understanding how to optimize lipid-loading onto antigen-presenting cells, to better harness iNKT cells central role at the interface between innate and adaptive immunity.