Fatty acid composition of chylomicron remnant‐like particles influences their uptake and induction of lipid accumulation in macrophages

Abstract

The first visible lesions in atherosclerosis development are fatty streaks, which are formed when macrophages that have invaded the artery wall take up lipid from plasma lipoproteins in the subendothelial space and become so engorged that they form foam cells [1]. It is known that low-density lipoprotein (LDL) has a major role in the induction of foam cell formation, but it is also clear that oxidation of the LDL particles, a process that can occur within the artery wall, is necessary before extensive lipid accumulation occurs [2]. Recent work in our laboratory and others, however, has provided strong evidence that chylomicron remnants, the lipoproteins that carry fat and cholesterol from the diet, are also able to induce macrophages to form foam cells, and furthermore, that prior oxidation of the particles is not required for their effect [3][4][5].

Modulation of Macrophage Fatty Acid Content and Composition by Exposure to Dyslipidemic Serum in Vitro

“…CRLP are pro-atherogenic being able to induce macrophage to form foam cells without prior oxidation [15]. Therefore, our work is consistent with previous studies in which CRLP enriched with saturated and monounsaturated FA are taken up more rapidly by macrophages, resulting in greater lipid accumulation of saturated FA [16]. The findings that ABCA1 as well as ABCG1 mRNA and protein levels decreased are consistent with the observation of Moore et al [17] in which lipid accumulated after exposure of macrophages to CRLP is resistant to efflux.…”

Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies

“…ApoCIII, a component of triglyceride-rich lipoproteins and an inhibitor of lipoprotein lipase activity, increases adhesion of monocytic cells to endothelial cells (49). Chylomicron remnants and triglyceride-rich lipoproteins also produce lipid accumulation in macrophages (50). Uptake of larger lipid-rich VLDL particles is favored in macrophages, promoting lipid accumulation (51).…”

“…The fatty acid composition of chylomicron remnants influences their uptake, and the induction of lipid accumulation in macrophages (50). The ability of triglyceride-rich lipoprotein particles to induce an inflammatory phenotype in macrophages may be enhanced by lipolytic release of fatty acids from VLDL (50;55).…”

Chylomicrons: A Key Biomarker and Risk Factor for Cardiovascular Disease and for the Understanding of Obesity

“…Once monocytes reside within the arterial wall, they differentiate into macrophages with subsequent risk of turning into highly atherogenic foam cells [50]. Importantly, chylomicron remnants can induce foam cell formation without the need to become modified, in contrast to native LDL [51,52]. In this respect, chylomicron remnants may be the most atherogenic lipoproteins in human physiology and, therefore, chylomicron remnant accumulation should be considered a relevant factor contributing to cardiovascular risk.…”