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Dobbiamo rivedere il metabolismo delle HDL?

Il metabolismo delle HDL inizia con la secrezione nel plasma di piccole particelle discoidali (prebeta-1) che hanno un basso contenuto in colesterolo non esterificato. Le particelle si arricchiscono in colesterolo libero di provenienza cellulare, il colesterolo viene esterificato per opera della lecitina:colesterolo aciltransferasi e durante questo processo le particelle assumono la forma sferica. Le HDL trasferiscono poi gli esteri del colesterolo alle LDL e VLDL per mezzo della proteina di trasporto lipidico (CETP) e al fegato tramite il recettore epatico SR-B1. Si rigenerano così HDL discoidali che ricominciano il ciclo. Questo in sintesi è il metabolismo delle HDL cui siamo abituati e le HDL circolanti con dimensioni e composizione diverse non sono altro che l'espressione di stadi successivi del loro metabolismo. Mendivil e coll. propongono una visione diversa e cioè che le varie sottofrazioni delle HDL sono secrete e circolano nel plasma nelle stesse dimensioni e vengono poi rimosse entro 1-4 giorni. In altri termini, le grosse HDL non sarebbero il prodotto della maturazione delle HDL discoidali nascenti, ma verrebbero secrete come tali.

Novel Pathways of Apolipoprotein A-I Metabolism in High-Density Lipoprotein of Different Sizes in Humans

Mendivil CO, Furtado J, Morton AM, Wang L, Sacks FM

Arterioscler Thromb Vasc Biol 2016;36:156-165

OBJECTIVE: A prevailing concept is that high-density lipoprotein (HDL) is secreted into the systemic circulation as a small mainly discoidal particle, which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans.
APPROACH AND RESULTS:We studied the metabolism of apolipoprotein A-I in 4 standard HDL sizes by endogenous isotopic labeling in 6 overweight adults with low HDLc and in 6 adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apolipoprotein A-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1 to 4 days and then was cleared. Enlargement of very small and medium to large and very large HDL and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower, whereas medium, large, and very large HDL were cleared faster in the low HDLc group.
CONCLUSIONS: A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes across the common range of HDLc concentrations.

Arterioscler Thromb Vasc Biol 2016;36:156-165