Lipid metabolic disorders play critical roles in atherogenesis. Traditionally, it has been suggested that reduced high density lipoprotein (HDL) levels might be an important morbidity indicator for cardiovascular diseases. Therefore, it has been argued that therapeutically raising HDL levels may reduce atherogenesis in patients with dyslipidemia. However, recent clinical trials to elevate serum HDL levels by pharmacological approaches failed to demonstrate clinical efficacy. Thus, to investigate the functionality of HDL and to explore the possible clinical relevance as well as to define an effective indicator that can represent HDL function may provide another key and reference to disclose the clinical treatment of dyslipidemia. We analyzed the association between the data of dichorofluorescein assay (assay the functionality of HDL), the effect of HDL on oxLDL-stimulated EPCs in vitro, levels of circulating EPCs, and ex vitro EPC colony forming units (CFUs) of each case, we defined the indicator (relative HDL index (RHDL index)=DCF result of each subject/DCF reading of our young healthy controls) that may represent functionality of HDL. HDL from healthy adults protected oxLDL-treated EPCs by modulating p38 mitogen-activated protein kinase and Rho activation and by promoting nitric oxide production. HDL from subject with RHDL index≧2 also failed to restore the functionality of oxLDL-treated EPCs via cell-signaling pathways in vitro. The RHDL index significantly correlated with patients’ circulating EPC number or EPC CFU ex vivo. In conclusions, we explored the RHDL index as a score to predict a patient’s EPC functions in vivo and ex vitro.
|Effective start/end date||8/1/17 → 7/31/18|
- oxidized low density lipoprotein
- high density lipoprotein
- p38 MAPK
- endothelial progenitor cell