The association between triglyceride-rich lipoproteins, circulating leukocytes, and low-grade inflammation: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Triglyceride-rich lipoproteins (TRLs) have been causally implicated in atherosclerotic cardiovascular disease (ASCVD) in epidemiological and mendelian randomization studies.1, 2, 3 Different pathophysiological mechanisms have been proposed to explain the atherogenicity of TRLs and their remnants.1 TRLs smaller than ∼70 nm can pass through the endothelium and accumulate in the subintimal compartment, contributing to foam cell formation and the sequence of events that lead to the atheroma plaque development.1 TRL-driven inflammation may also potentiate atherogenesis. In experimental studies, lipolysis-generated free fatty acids and oxidized phospholipids can elicit pro-inflammatory effects in endothelial cells and macrophages,1,4,5 and apolipoprotein CIII activates the NLRP3 inflammasome in human monocytes.6 TRLs induce activation of circulating neutrophils and monocytes,7,8 and may be involved in the formation of pro-inflammatory foamy monocytes in the circulation.9 Moreover, there is genetic evidence of a causal relationship between elevated levels of nonfasting remnant cholesterol, a surrogate marker of TRL concentration, and higher high-sensitivity C-reactive protein (hs-CRP) levels in humans.3

Therefore, the cumulative evidence supports that TRLs per se may contribute to the so-called meta-inflammation, i.e., the low-grade chronic inflammation associated with obesity and related metabolic disorders.10 However, TRLs are highly heterogeneous in size and composition. It is not well known which TRL subparticles are responsible for the TRL pro-inflammatory effects in the general population. Also, the role of leukocyte activation in mediating TRL pro-inflammatory actions has not been fully addressed. In this study, we investigated whether TRLs (total number and subparticles) are independently associated with circulating leukocytes and plasma levels of hs-CRP and GlycA, a newer inflammatory biomarker reflecting the aggregated levels of several glycosylated acute-phase proteins.11,12

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