Header

UZH-Logo

Maintenance Infos

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


Adams, Volker; Besler, Christian; Fischer, Tina; Riwanto, Meliana; Noack, Friederike; Höllriegel, Robert; Oberbach, Andreas; Jehmlich, Nico; Volker, Uwe; Winzer, Ephraim B; Lenk, Karsten; Hambrecht, Rainer; Schuler, Gerhard C; Linke, Axel; Landmesser, Ulf; Erbs, Sandra (2013). Exercise training in patients with chronic heart failure promotes restoration of HDL functional properties. Circulation Research, 113(12):1345-1355.

Abstract

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

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.

Statistics

Citations

26 citations in Web of Science®
30 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

144 downloads since deposited on 18 Nov 2013
49 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:18 Nov 2013 16:08
Last Modified:05 Apr 2016 17:05
Publisher:Lippincott, Williams & Wilkins
ISSN:0009-7330
Additional Information:This is a non-final version of an article published in final form in Circulation Research 2013, Epub ahead of print.
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/CIRCRESAHA.113.301684
PubMed ID:24055733

Download

Download PDF  'Exercise training in patients with chronic heart failure promotes restoration of HDL functional properties'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 535kB
View at publisher