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-Ser1177, eNOS-Thr495, PKC-ßII-Ser660 and p70S6K-Ser411 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-Ser1177 and a higher phosphorylation at eNOS-Thr495 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.
- endothelial dysfunction
- heart failure
- high-density lipoprotein
- endothelial nitric oxide synthase
- exercise training
- Received April 26, 2013.
- Revision received September 17, 2013.
- Accepted September 20, 2013.