Exercise training in patients with chronic heart failure promotes restoration of HDL functional properties

: Rationale: HDL exerts endothelial-protective effects via stimulation of endothelial cell (EC) NO production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated Objective: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF). Methods and Results: HDL was isolated from 16 healthy controls (HDLhealthy) and 16 patients with CHF-NYHA-III (HDLNYHA-IIIb) before and after ET, and 8 patients with CHF-NYHA-II (HDLNYHA-II). EC were incubated with HDL and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-ßII-Ser(660) and p70S6K-Ser(411) was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation (FMD). The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDLNYHA-IIIb triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared to HDLhealthy. This was associated with lower NO production of EC. In addition an elevated activation of p70S6K, PKC-ßII by HDLNYHA-IIIb, and a higher amount of malondialdehyde bound to HDLNYHA-IIIb compared to HDLhealthy was measured. In healthy individuals ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIB significantly improved HDL function. A correlation between changes in HDL-induced NO production and FMD improvement by ET was evident. Conclusions: These results demonstrate that HDL-function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF. Abstract: Background: HDL exerts endothelial-protective effects via stimulation of endothelial cell NO production. This function is impaired in patients with cardiovascular disease. Studies demonstrated that exercise training (ET) has protective effects on endothelial function. Aim of this study was to evaluate HDL function in patients with chronic heart failure (CHF), the impact of ET and the respective molecular pathways. Methods: HDL was isolated from 8 healthy controls (HDL healthy ) before and after ET, , 8 patients with CHF-NYHA-II (HDL NYHA-II ), and 8 patients with CHF-NYHA-IIIB (HDL NYHA-IIIb ) before and after ET. Endothelial cells (EC) were incubated with HDL and phosphorylation of eNOS-Ser 1177 , eNOS-Thr 495 , PKC-ßII-Ser 660 and p70S6K-Ser 411 was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC was quantified. The proteome of HDL particles were investigated by shotgun LC-MS/MS. Endothelial function was assessed by flow-mediated dilatation (FMD). Results: Incubation of ECs with HDL NYHA-IIIb reduced phosphorylation of eNOS-Ser 1177 , whereas phosphorylation at eNOS-Thr 495 increased when compared to HDL healthy . This was associated with lower NO production of ECs incubated with HDL NYHA-IIIb . In addition an elevated activation of p70S6K, PKC-ßII by HDL NYHA-IIIb , and a higher amount of malondialdehyde bound to HDL NYHA-IIIb was measured. correlation between in