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I trigliceridi modificano il metabolismo degli esteri del colesterolo nella cellula schiumosa

Il colesterolo depositato nei lisosomi è il maggiore costituente lipidico delle cellule schiumose ed è difficilmente rimovibile. La presenza di trigliceridi nella cellula rende più facile la rimozione del colesterolo lisosomiale.

Triglyceride alters lysosomal cholesterol metabolism in cholesteryl ester-laden macrophage foam cells

Ullery-Ricewick JC, Cox BE, Griffin EE, Jerome WG.

J Lipid Res 2009;50:2014-26

In late stage atherosclerosis, much of the cholesterol in macrophage foam cells resides within enlarged lysosomes. Similarly, human macrophages incubated in vitro with modified LDLs contain significant amounts of lysosomal free cholesterol (FC) and cholesteryl ester (CE), which disrupts lysosomal function similar to macrophages in atherosclerotic lesions. The lysosomal cholesterol cannot be removed, even in the presence of strong efflux promoters. Thus, efflux of sterol is prevented. In the artery wall, foam cells interact with triglyceride-rich particles (TRP) in addition to modified LDLs. Little is known about how TRP metabolism affects macrophage cholesterol. Therefore, we explored the effect of TRP on intracellular CE metabolism. Triglyceride (TG), delivered to lysosomes in TRP, reduced CE accumulation by 50%. Increased TG levels within the cell, particularly within lysosomes, correlated with reductions in CE content. The volume of cholesterol-engorged lysosomes decreased after TRP-treatment, indicating cholesterol was cleared. Lysosomal TG also reduced the cholesterol-induced inhibition of lysosomal acidification allowing lysosomes to remain active. Enhanced degradation and clearance of CE may be explained by movement of cholesterol out of the lysosome to sites where it is effluxed. Thus, our results show that introduction of TG into CE-laden foam cells influences CE metabolism and, potentially, atherogenesis.