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Exercise training improves HDL quality in CHF patients

Comment by Nicolle Kraenkel, EACPR Exercise, Basic and Translational Research Section

Cardiovascular Rehabilitation

High-density lipoprotein (HDL) is generally believed to exert only beneficial effects onto the cardiovascular system. Yet, pure elevation of HDL levels in patients with recent acute cardiac syndrome was not sufficient to reduce risk of recurrent cardiovascular events (1).

Instead, accumulating evidence indicates that HDL composition and post-translational modifications, such as oxidation state, play an important role in HDL effects on endothelial cells (2).

In their recent study, Adams et al. have investigated the effects of a 12-week exercise-based cardiac rehabilitation programme in patients with NYHA class IIIb congestive heart failure (CHF) on the endothelial effects of patients' HDL. As a control group, healthy participants performed a 4-week exercise training protocol of comparable total exercise time and volume.

Initially, HDL from CHF patients induced nitric oxide generation in endothelial cells less efficiently than HDL from health study participants, which was associated with higher levels of limiting endothelial nitric oxide synthase (eNOS) phosphorylation state at Thr495 and lower levels of activting phosphorylation at Ser1177. At the end of the exercise programme, HDL-induced nitric oxide generation, as well as eNOS phosphorylation state was improved in exercising CHF patients, but not in healthy participants.

Interestingly, while HDL proteome significantly differed from HDL of healthy paticipants, exercise training did not induce significant alterations in patients' HDL, thus not sufficiently explaining the functional rescue. The same was observed for activity of the HDL-associated antioxidant paraoxonase-1.  Only HDL-bound malondialdehyde, a marker of oxidative stress, was reduced by exercise in CHF patients.

The authors thus speculate that in patients with severe CHF, exercise training achieves a "lightening of the burden" of systemic  pro-oxidant status and inhibition of nitric oxide generation, rather than actively upregulating anti-oxidant pathways, as least as far as HDL is concerned.

Although several studies have undertaken proteomic analysis of HDL quality changes in various patient cohorts, the HDL particle still remains a black box whose cargo is dynamically altered in various physiologic and pathologic states. The findings of most studies remain mainly descriptive without efficient translation into therapy. Exercise training once more offers a pleiotropic approach to reduce pro-oxidant and pro-inflammatory load on a systemic level.

In this study, a partial rescue of HDL function was achieved, rather by suspending some of the pro-oxidant and pro-inflammatory mechanisms active in CHF than by actively enhancing e.g. the anti-oxidant activity of paraoxonase. It remains open whether longer duration of the exercise programme, or combination with pharmacologic interventions could further modulate HDL quality and function.

Nevertheless, HDL is only one mediator among many - shear stress, circulating inflammatory cytokines, growth factors and more - which in combination effect the improvement of endothelial function in vivo.


  1. Effects of dalcetrapib in patients with a recent acute coronary syndrome. Schwartz GG et al.
    N Engl J Med. 2012;367:2089
  2. Altered activation of endothelial anti- and proapoptotic pathways by high-density lipoprotein from patients with coronary artery disease: role of high-density lipoprotein-proteome remodeling. Riwanto M et al.
    Circulation. 2013;127:891