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Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males.
Arterioscler Thromb Vasc Biol. 1997 Oct; 17(10):1910-7.AT

Abstract

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.

Authors+Show Affiliations

Lipid Research Laboratory, New England Medical Center, Boston, MA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9351353

Citation

Cuchel, M, et al. "Lovastatin Decreases De Novo Cholesterol Synthesis and LDL Apo B-100 Production Rates in Combined-hyperlipidemic Males." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 10, 1997, pp. 1910-7.
Cuchel M, Schaefer EJ, Millar JS, et al. Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males. Arterioscler Thromb Vasc Biol. 1997;17(10):1910-7.
Cuchel, M., Schaefer, E. J., Millar, J. S., Jones, P. J., Dolnikowski, G. G., Vergani, C., & Lichtenstein, A. H. (1997). Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males. Arteriosclerosis, Thrombosis, and Vascular Biology, 17(10), 1910-7.
Cuchel M, et al. Lovastatin Decreases De Novo Cholesterol Synthesis and LDL Apo B-100 Production Rates in Combined-hyperlipidemic Males. Arterioscler Thromb Vasc Biol. 1997;17(10):1910-7. PubMed PMID: 9351353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males. AU - Cuchel,M, AU - Schaefer,E J, AU - Millar,J S, AU - Jones,P J, AU - Dolnikowski,G G, AU - Vergani,C, AU - Lichtenstein,A H, PY - 1997/11/14/pubmed PY - 1997/11/14/medline PY - 1997/11/14/entrez SP - 1910 EP - 7 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 17 IS - 10 N2 - The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed. SN - 1079-5642 UR - https://www.unboundmedicine.com/medline/citation/9351353/Lovastatin_decreases_de_novo_cholesterol_synthesis_and_LDL_Apo_B_100_production_rates_in_combined_hyperlipidemic_males_ L2 - https://www.ahajournals.org/doi/10.1161/01.atv.17.10.1910?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -