Exercise training in patients with chronic heart failure promotes restoration of high-density lipoprotein functional properties.
BACKGROUND
High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (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).


RESULTS
HDL was isolated from 16 healthy controls (HDL(healthy)) and 16 patients with CHF-NYHA-III (HDL(NYHA-IIIb)) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDL(NYHA-II)). ECs were incubated with HDL, and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-βII-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. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDL(NYHA-IIIb) triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared with HDL(healthy). This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-βII by HDL(NYHA-IIIb), and a higher amount of malondialdehyde bound to HDL(NYHA-IIIb) compared with HDL(healthy) 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 flow-mediated dilatation 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.
From the Departments of Cardiology (V.A., T.F., F.N., R.H., E.B.W., K.L., G.S., A.L., S.E.) and Cardiac Surgery (A.O.), Heart Center Leipzig, Leipzig University, Germany; Department of Cardiology, University Hospital Zürich, Switzerland (C.B., M.R., U.L.); Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Germany (N.J., U.V.); DZHK (German Center for Cardiovascular Research), Greifswald, Germany (U.V.); and Klinikum Links der Weser, Heart Center Bremen, Germany (R.H.).
Volker
V
Adams
Christian
C
Besler
Tina
T
Fischer
Meliana
M
Riwanto
Friederike
F
Noack
Robert
R
Höllriegel
Andreas
A
Oberbach
Nico
N
Jehmlich
Uwe
U
Völker
Ephraim B
EB
Winzer
Karsten
K
Lenk
Rainer
R
Hambrecht
Gerhard
G
Schuler
Axel
A
Linke
Ulf
U
Landmesser
Sandra
S
Erbs
D000368:Aged; D002478:Cells, Cultured; D002908:Chronic Disease; D015331:Cohort Studies; D005080:Exercise Test / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D064797:Physical Conditioning, Human / Q000502:physiology*
D008075:Lipoproteins, HDL
aerobic exercise; eNOS; lipoproteins, HDL