Dietary interventions and HDL anti-inflammatory activity: the potential to modulate macrophage polarization

Abstract

Lowering LDL cholesterol (LDL-C) is the primary clinical approach to prevent cardiovascular events and is often achieved with statin therapy. However, even patients treated with statins have a considerable residual burden of cardiovascular risk, highlighting the need to address risk factors beyond LDL-C, such as inflammation and oxidative stress. Increasing attention has also focused on HDL functionality as a cardioprotective approach. Data from our international collaborators have shown that HDL can lead to a shift in macrophages phenotype from an inflammatory state (M1) towards an anti-inflammatory state (M2), in vivo and in vitro, and that polarization to the M2 state is required for resolution of atherosclerotic inflammation and plaque regression. However, this potential is attributed only to "functional" HDL particles. Impaired HDL function has been mainly associated with oxidative modifications, though particle fatty acid composition may also play important roles in anti-inflammatory activity of HDL. As omega 3 fatty acids have (n-3 FA) been shown to modulate macrophage inflammation, we hypothesized that HDL enrichment with n-3 FA can increase anti-inflammatory activity of HDL, what would be especially important in the context of cardiovascular disease management. In a previous study from our research group we showed that combined intake of n-3 FA, plant sterols and polyphenols reduces inflammation, lipemia and oxidative stress in statin-treated patients, which are important biomarker changes that contribute to increased cardiovascular protection. Therefore, we now propose to investigate the anti-inflammatory activity of HDL fractions isolated from human plasma after intake of the combined bioactive treatment, along with additional in vitro and ex vivo experiments. The understanding of mechanisms that increase HDL anti-inflammatory activity through natural compounds will provide further knowledge on the potential of dietary co-therapy to reduce cardiovascular events and may also provide insight into pharmacological and nanotechnology applications. (AU)