Abstract

The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to atherosclerosis in a free-living population with a high-risk of cardiovascular disease (CD). Participants (n = 285) in the PREDIMED trial were randomly assigned into three intervention groups: MD with extra-virgin olive oil (EVOO) or MD-Nuts, and a LFD. Fourteen plasma inflammatory biomarkers were determined by Luminex assays. An additional pilot study of gene expression (GE) was determined by RT-PCR in 35 participants. After 3 years, both MDs showed a significant reduction in the plasma levels of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, hs-CRP, MCP-1, MIP-1β, RANTES, and ENA78 (p < 0.05; all). The decreased levels of IL-1β, IL-6, IL-8, and TNF-α after MD significantly differed from those in the LFD (p < 0.05). No significant changes were observed at the gene level after MD interventions, however, the GE of CXCR2 and CXCR3 tended to increase in the control LFD group (p = 0.09). This study supports the implementation of MD as a healthy long-term dietary pattern in the prevention of CD in populations at high cardiovascular risk.

Highlights

  • Atherosclerosis is the leading cause of death (31%) and the primary initiator of two major morbidities worldwide: Coronary and cerebrovascular diseases [1]

  • The PREDIMED study is a parallel-group, single-blind, multicenter, randomized, controlled 5-year clinical trial aimed to assess the effects of a Mediterranean diet (MD)-extra-virgin olive oil (EVOO) or mixed nuts (MD-Nuts) on the primary prevention of cardiovascular diseases compared with a control low-fat diet (LFD)

  • We found a positive correlation between ENA78 and different chemokines with both MDs (Table 2) which were not observed in the LFD group for MCP-1 and MIP-1β

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Summary

Introduction

Atherosclerosis is the leading cause of death (31%) and the primary initiator of two major morbidities worldwide: Coronary and cerebrovascular diseases (http://www.who.int/cardiovascular_diseases/en/, accessed on 19 April 2021) [1]. Recent studies indicate that the cell surface receptor CD36 facilitates internalization of oxidized LDL (oxLDL) and intracellular conversion of oxLDL to cholesterol crystals which are able to activate the Nod-like receptor protein (NLRP) 3 inflammasome in vitro experiments through its bond to toll-like receptors (TLRs) [2,3,4,5,6]. This process leads to the recruitment of leukocytes and a higher expression of adhesion molecules such as. This activation leads to the maturation of caspase-1 and the processing of its substrates, interleukin (IL)-1β and IL-18 [2,6,12], and IL-1β promotes the development of lipid plaque and destabilizes it [6,13]

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