Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships with Fluidity of HDL Monolayer

Abstract

Scope Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion. Methods and Results Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity. Conclusions HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions.

Relationship Between HDL Functional Characteristics and Cardiovascular Health and Potential Impact of Dietary Patterns: A Narrative Review

“…Virgin olive oil and whole grains were independently associated with increased cholesterol efflux capacity, nuts and legumes were independently associated with increased PON1 antioxidant activity, and fish consumption was associated with increased PON1 and decreased CETP activity. This supports the limited existing data of other food interventions (virgin olive oil, lycopene-rich diet, nuts and eggs) within a healthy diet that have been shown to increase HDL functionality [78,79,80,81,82].…”

Cardiovascular Benefits of Phenol‐Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study

“…These changes resulted in the enhancement of CEC, among other functions . Accordingly, in the VOHF study, we have described that a decrease in free cholesterol and an increase in triglycerides are major determinants of monolayer fluidity and therefore of CEC …”

“…Moreover, in a cohort of asymptomatic older adults, CEC was inversely associated with s‐HDL particle levels and was directly associated with l‐HDL, medium HDL, and HDL size . In concordance with this evidence, in the VOHF study, we have found that CEC was directly related to HDL size, with s‐HDL being inversely related to CEC . This paradoxical evidence on the presence of high levels of s‐HDL in CVD, together with s‐HDL being more functional than l‐HDL, may be explained by the hypothesis that increased s‐HDL particles in the serum may indicate an aberration in the maturation of s‐HDL particles, therefore increasing the risk of CVD .…”

A Functional Virgin Olive Oil Enriched with Olive Oil and Thyme Phenolic Compounds Improves the Expression of Cholesterol Efflux-Related Genes: A Randomized, Crossover, Controlled Trial

“…Among its beneficial mechanisms, the intake of olive oil PCs has been shown to promote major high-density lipoprotein (HDL) function, particularly cholesterol efflux capacity (HDL’s ability to pick up cholesterol from macrophages), as well as other improvements in HDL quality characteristics [5]. Going one step further, the consumption of enriched or functional VOOs, supplemented with olive oil PCs or other complementary PCs such as those from thyme, has also been shown to improve HDL functional traits and lipid profile [6,7,8,9,10], as well as other molecular mechanisms potentially involved in the development of cardiovascular diseases [11,12]. On the one hand, olive oil PCs are essentially monophenols such as hydroxytyrosol and tyrosol, whose effect on cardiovascular protection [13] (mainly based on their capacity to neutralize pro-oxidant substances) may be complemented with that from more complex PCs such as flavonoids (known to also be able to directly modulate pro-inflammatory pathways such as those involving phosphoinositol-3-kinase/protein kinase B, protein kinase C, and mitogen-activated protein kinases [14]).…”