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L'apo A-II regola la trigliceridemia attraverso la lipasi lipoproteica

La quantità di apo A-II nelle HDL è inversamente correlata con la trigliceridemia basale e postprandiale. Come suggerito dai risultati di studi su topi transgenici, è verosimile che l'azione di modulazione della trigliceridemia da parte dell'apo A-II sia mediata dall'effetto inibitorio dell'apoproteina sulla lipasi lipoproteica. L'azione inibitoria non sarebbe comunque diretta, ma è dovuta al fatto che nelle HDL l'apo A-II va a rimpiazzare, almeno in parte, l'apo C-II che è il fisiologico attivatore della lipasi lipoproteica. studi.

Human apolipoprotein A-II determines plasma triglycerides by regulating lipoprotein lipase activity and high-density lipoprotein proteome

Julve J, Escolà-Gil JC, Rotllan N, Fiévet C, Vallez E, de la Torre C, Ribas V, Sloan JH, Blanco-Vaca F.

Arterioscler Thromb Vasc Biol 2010;30:232-238

INTRODUCTION: Apolipoprotein (apo) A-II is the second most abundant high-density lipoprotein (HDL) apolipoprotein. We assessed the mechanism involved in the altered postprandial triglyceride-rich lipoprotein metabolism of female human apoA-II-transgenic mice (hapoA-II-Tg mice), which results in up to an 11-fold increase in plasma triglyceride concentration. The relationships between apoA-II, HDL composition, and lipoprotein lipase (LPL) activity were also analyzed in a group of normolipidemic women. METHODS AND RESULTS: Triglyceride-rich lipoprotein catabolism was decreased in hapoA-II-Tg mice compared to control mice. This suggests that hapoA-II, which was mainly associated with HDL during fasting and postprandially, impairs triglyceride-rich lipoprotein lipolysis. HDL isolated from hapoA-II-Tg mice impaired bovine LPL activity. Two-dimensional gel electrophoresis, mass spectrometry, and immunonephelometry identified a marked deficiency in the HDL content of apoA-I, apoC-III, and apoE in these mice. In normolipidemic women, apoA-II concentration was directly correlated with plasma triglyceride and inversely correlated with the HDL-apoC-II+apoE/apoC-III ratio. HDL-mediated induction of LPL activity was inversely correlated with apoA-II and directly correlated with the HDL-apoC-II+apoE/apoC-III ratio. Purified hapoA-II displaced apoC-II, apoC-III, and apoE from human HDL2. Human HDL3 was, compared to HDL2, enriched in apoA-II but poorer in apoC-II, apoC-III, and apoE. CONCLUSIONS: ApoA-II plays a crucial role in triglyceride catabolism by regulating LPL activity, at least in part, through HDL proteome modulation.

Arterioscler Thromb Vasc Biol 2010;30:232-238