Abstract

High-density lipoproteins (HDL) maintain cholesterol homeostasis through the role they play in regulating reverse cholesterol transport (RCT), a process by which excess cholesterol is transported back to the liver for elimination. However, RCT can be altered in the presence of cardiovascular risk factors, such as aging, which contributes to the increase in the incidence of cardiovascular diseases (CVD). The present study was aimed at investigating the effect of extra virgin olive oil (EVOO) intake on the cholesterol efflux capacity (CEC) of HDL, and to elucidate on the mechanisms by which EVOO intake improves the anti-atherogenic activity of HDL. A total of 84 healthy women and men were enrolled and were distributed, according to age, into two groups: 27 young (31.81 ± 6.79 years) and 57 elderly (70.72 ± 5.6 years) subjects. The subjects in both groups were given 25 mL/d of extra virgin olive oil (EVOO) for 12 weeks. CEC was measured using J774 macrophages radiolabeled with tritiated cholesterol ((3H) cholesterol). HDL subclass distributions were analyzed using the Quantimetrix Lipoprint® system. The HDL from the elderly subjects exhibited a lower level of CEC, at 11.12% (p < 0.0001), than the HDL from the young subjects. The CEC of the elderly subjects returned to normal levels following 12 weeks of EVOO intake. An analysis of the distribution of HDL subclasses showed that HDL from the elderly subjects were composed of lower levels of large HDL (L-HDL) (p < 0.03) and higher levels of small HDL (S-HDL) (p < 0.002) compared to HDL from the young subjects. A multiple linear regression analysis revealed a positive correlation between CEC and L-HDL levels (r = 0.35 and p < 0.001) as well as an inverse correlation between CEC and S-HDL levels (r = −0.27 and p < 0.01). This correlation remained significant even when several variables, including age, sex, and BMI as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glucose levels (β = 0.28, p < 0.002, and β = 0.24, p = 0.01) were accounted for. Consuming EVOO for 12 weeks modulated the age-related difference in the distribution of HDL subclasses by reducing the level of S-HDL and increasing the level of intermediate-HDL/large-HDL (I-HDL/L-HDL) in the elderly subjects. The age-related alteration of the CEC of HDL was due, in part, to an alteration in the distribution of HDL subclasses. A diet enriched in EVOO improved the functionality of HDL through an increase in I-HDL/L-HDL and a decrease in S-HDL.

Highlights

  • Cardiovascular disease (CVD) is one of the major causes of mortality and morbidity in developed, middle, and low income countries [1]

  • We investigated the effect of extra virgin olive oil (EVOO) intake as a function of the age of the particWe investigated the effect of EVOO intake as a function of the age of the particiipants on the distribution of the high-density lipoproteins (HDL) subclasses

  • Our results showed that EVOO intake significantly improved the cholesterol efflux capacity (CEC) of HDL in the elderly, bringing it to levels similar to that measured for HDL from young people

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Summary

Introduction

Cardiovascular disease (CVD) is one of the major causes of mortality and morbidity in developed, middle, and low income countries [1]. The incidence of atherosclerotic cardiovascular disease (ASCVD) increases dramatically with advancing age and constitutes the main cause of mortality and morbidity in the elderly [2]. Pharmacological interventions aimed at increasing HDL levels were disappointing in terms of cardiovascular protection and have raised doubts about the relevance of HDL as an ideal target for atheroprotective therapies [7]. This approach led to the emergence of the concept that the functionality or quality of HDL is much more important for some patients than HDL levels with respect to cardiovascular protection [8]

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