Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia

Claudio Napoli, Maurizio Leccese, Giuseppe Palumbo, Filomena De Nigris, Paola Chiariello, Patrizia Zuliani, Pasquale Somma, Mario Di Loreto, Carmine De Matteis, Francesco Cacciatore, Pasquale Abete, Antonio Liguori, Massimo Chiariello, Francesco P. D'Armiento

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background. The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl esters to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for use in anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. Objective. To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. Methods. This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and pravastatin in combination with 100 mg/day vitamin E (100 IU) as DL-α-tocopherol (n = 56), diet and α-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. Results. The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P <0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P <0.05). No significant differences in the plasma activity of LCAT were observed among the groups. Conclusions. Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Original languageEnglish
Pages (from-to)257-264
Number of pages8
JournalCoronary Artery Disease
Volume9
Issue number5
Publication statusPublished - 1998

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Cholesterol Ester Transfer Proteins
Phosphatidylcholine-Sterol O-Acyltransferase
Hydroxymethylglutaryl CoA Reductases
Lecithins
Hypercholesterolemia
Vitamin E
Transferases
Pravastatin
Cholesterol
Diet
Cholesterol Esters
LDL Lipoproteins
Tocopherols
Blood Proteins
Hyperlipoproteinemia Type III
Antioxidants
Placebos
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Simvastatin
VLDL Lipoproteins

Keywords

  • Antioxidants
  • Atherosclerosis
  • CETP
  • Hypercholesterolemia
  • LCAT
  • Oxygen radicals
  • Pravastatin
  • Vitamin E

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia. / Napoli, Claudio; Leccese, Maurizio; Palumbo, Giuseppe; De Nigris, Filomena; Chiariello, Paola; Zuliani, Patrizia; Somma, Pasquale; Di Loreto, Mario; De Matteis, Carmine; Cacciatore, Francesco; Abete, Pasquale; Liguori, Antonio; Chiariello, Massimo; D'Armiento, Francesco P.

In: Coronary Artery Disease, Vol. 9, No. 5, 1998, p. 257-264.

Research output: Contribution to journalArticle

Napoli, C, Leccese, M, Palumbo, G, De Nigris, F, Chiariello, P, Zuliani, P, Somma, P, Di Loreto, M, De Matteis, C, Cacciatore, F, Abete, P, Liguori, A, Chiariello, M & D'Armiento, FP 1998, 'Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia', Coronary Artery Disease, vol. 9, no. 5, pp. 257-264.
Napoli, Claudio ; Leccese, Maurizio ; Palumbo, Giuseppe ; De Nigris, Filomena ; Chiariello, Paola ; Zuliani, Patrizia ; Somma, Pasquale ; Di Loreto, Mario ; De Matteis, Carmine ; Cacciatore, Francesco ; Abete, Pasquale ; Liguori, Antonio ; Chiariello, Massimo ; D'Armiento, Francesco P. / Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia. In: Coronary Artery Disease. 1998 ; Vol. 9, No. 5. pp. 257-264.
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abstract = "Background. The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl esters to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for use in anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. Objective. To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. Methods. This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and pravastatin in combination with 100 mg/day vitamin E (100 IU) as DL-α-tocopherol (n = 56), diet and α-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. Results. The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P <0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P <0.05). No significant differences in the plasma activity of LCAT were observed among the groups. Conclusions. Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.",
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TY - JOUR

T1 - Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia

AU - Napoli, Claudio

AU - Leccese, Maurizio

AU - Palumbo, Giuseppe

AU - De Nigris, Filomena

AU - Chiariello, Paola

AU - Zuliani, Patrizia

AU - Somma, Pasquale

AU - Di Loreto, Mario

AU - De Matteis, Carmine

AU - Cacciatore, Francesco

AU - Abete, Pasquale

AU - Liguori, Antonio

AU - Chiariello, Massimo

AU - D'Armiento, Francesco P.

PY - 1998

Y1 - 1998

N2 - Background. The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl esters to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for use in anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. Objective. To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. Methods. This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and pravastatin in combination with 100 mg/day vitamin E (100 IU) as DL-α-tocopherol (n = 56), diet and α-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. Results. The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P <0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P <0.05). No significant differences in the plasma activity of LCAT were observed among the groups. Conclusions. Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

AB - Background. The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl esters to very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for use in anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. Objective. To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. Methods. This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and pravastatin in combination with 100 mg/day vitamin E (100 IU) as DL-α-tocopherol (n = 56), diet and α-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. Results. The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P <0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P <0.05). No significant differences in the plasma activity of LCAT were observed among the groups. Conclusions. Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

KW - Antioxidants

KW - Atherosclerosis

KW - CETP

KW - Hypercholesterolemia

KW - LCAT

KW - Oxygen radicals

KW - Pravastatin

KW - Vitamin E

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