The acute phase protein Haptoglobin (Hpt) binds ApoA-I and impairs its stimulation of Lecithin-Cholesterol Acyl-Transferase (LCAT), an enzyme playing a key role in an anti-atherosclerotic process called reverse cholesterol transport (RCT). LCAT converts cholesterol (C) into cholesteryl esters (CE) for HDL-mediated transport. Beyond the key role in RCT, the anti-inflammatory activity of ApoA-I is largely recognized. We previously reported that an ApoA-I mimetic peptide, P2a displaces Hpt from ApoA-I and restores the LCAT activity in vitro. Our aim was to study if P2a displaces Hpt from ApoA-I in vivo in inflamed mice and if this event is linked to an anti-inflammatory activity. Inflammation was induced by carrageenan injection. Cholesterol esterification significantly decreased in inflamed mice during oedema development and negatively correlated with Hpt/ApoA-I ratio. The administration of the peptide P2a significantly restored the C esterification. Also, P2a displays an anti-inflammatory effect on the late phase of oedema with a reduction in COX-2 expression coupled to an inhibition of PGE2, implying that, in presence of P2a, CE/C ratio rescue and oedema inhibition are related. We conclude that P2a, by virtue of its ability to bind Hpt, makes ApoA-I available to stimulate LCAT and to play its anti-inflammatory role. These data suggest that peptides able to displace Hpt might be useful in the treatment of inflammatory cardiovascular diseases such as atherosclerosis.
An Apolipoprotein A-I mimetic peptide improves reverse cholesterol transport during inflammation and unmasks Apo A-I anti-inflammatory activity in vivo / Cigliano, Luisa; Bucci, Mariarosaria; Carlucci, A.; D’Andrea, L. D.; Vellecco, V.; Ziaco, B.; Rossi, A.; Sautebin, L.; Pedone, Carlo; Cirino, G.; Spagnuolo, M. S.. - In: ACTA PHYSIOLOGICA. - ISSN 1748-1716. - ELETTRONICO. - (2011), pp. 228-228. (Intervento presentato al convegno 62nd National Congress of the Italian Physiological Society tenutosi a Sorrento nel 25-27 September 2011).
An Apolipoprotein A-I mimetic peptide improves reverse cholesterol transport during inflammation and unmasks Apo A-I anti-inflammatory activity in vivo.
CIGLIANO, LUISA;VELLECCO V.;PEDONE, CARLO;CIRINO G.;
2011
Abstract
The acute phase protein Haptoglobin (Hpt) binds ApoA-I and impairs its stimulation of Lecithin-Cholesterol Acyl-Transferase (LCAT), an enzyme playing a key role in an anti-atherosclerotic process called reverse cholesterol transport (RCT). LCAT converts cholesterol (C) into cholesteryl esters (CE) for HDL-mediated transport. Beyond the key role in RCT, the anti-inflammatory activity of ApoA-I is largely recognized. We previously reported that an ApoA-I mimetic peptide, P2a displaces Hpt from ApoA-I and restores the LCAT activity in vitro. Our aim was to study if P2a displaces Hpt from ApoA-I in vivo in inflamed mice and if this event is linked to an anti-inflammatory activity. Inflammation was induced by carrageenan injection. Cholesterol esterification significantly decreased in inflamed mice during oedema development and negatively correlated with Hpt/ApoA-I ratio. The administration of the peptide P2a significantly restored the C esterification. Also, P2a displays an anti-inflammatory effect on the late phase of oedema with a reduction in COX-2 expression coupled to an inhibition of PGE2, implying that, in presence of P2a, CE/C ratio rescue and oedema inhibition are related. We conclude that P2a, by virtue of its ability to bind Hpt, makes ApoA-I available to stimulate LCAT and to play its anti-inflammatory role. These data suggest that peptides able to displace Hpt might be useful in the treatment of inflammatory cardiovascular diseases such as atherosclerosis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.