Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine

Judith Hasler-Rapacz, Herman J. Kempen, Hans M.G. Princen, Bhalchandra J. Kudchodkar, Andras G. Lacko, Jan Rapacz

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG). LDL-cholesterol (LDL- C), apolipoproteins (apo) B, CIII, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals exhibiting TC≥250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL- C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25%). LDL-C (-27%), lathosterol (-40%), apoB (- 22%), apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (-12%) and apoA-I (-11%) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoa- I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC. LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swines is similar to that observed in humans, although the drug is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.

Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume16
Issue number1
DOIs
StatePublished - 1 Jan 1996

Fingerprint

Simvastatin
Apolipoproteins
Swine
Apolipoprotein A-I
Apolipoproteins B
Apolipoprotein C-III
Phosphatidylcholine-Sterol O-Acyltransferase
Lipids
HDL Cholesterol
Hyperlipoproteinemia Type II
Apolipoproteins E
Cholesterol
LDL Cholesterol
Triglycerides
Familial Combined Hyperlipidemia
VLDL Cholesterol
Lipoproteins
Coronary Disease
Oxidoreductases
oxidized low density lipoprotein

Keywords

  • animal model
  • apolipoproteins
  • familial hypercholesterolemia
  • simvastatin
  • swine

Cite this

Hasler-Rapacz, Judith ; Kempen, Herman J. ; Princen, Hans M.G. ; Kudchodkar, Bhalchandra J. ; Lacko, Andras G. ; Rapacz, Jan. / Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1996 ; Vol. 16, No. 1. pp. 137-143.
@article{e4e855bfc9ea47499298e3d5c5bccb48,
title = "Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine",
abstract = "Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG). LDL-cholesterol (LDL- C), apolipoproteins (apo) B, CIII, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals exhibiting TC≥250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL- C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25{\%}). LDL-C (-27{\%}), lathosterol (-40{\%}), apoB (- 22{\%}), apoC-III (-37{\%}), and apoE (-24{\%}) and modestly decreased the levels of HDL-C (-12{\%}) and apoA-I (-11{\%}) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoa- I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC. LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swines is similar to that observed in humans, although the drug is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.",
keywords = "animal model, apolipoproteins, familial hypercholesterolemia, simvastatin, swine",
author = "Judith Hasler-Rapacz and Kempen, {Herman J.} and Princen, {Hans M.G.} and Kudchodkar, {Bhalchandra J.} and Lacko, {Andras G.} and Jan Rapacz",
year = "1996",
month = "1",
day = "1",
doi = "10.1161/01.ATV.16.1.137",
language = "English",
volume = "16",
pages = "137--143",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "1",

}

Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine. / Hasler-Rapacz, Judith; Kempen, Herman J.; Princen, Hans M.G.; Kudchodkar, Bhalchandra J.; Lacko, Andras G.; Rapacz, Jan.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 16, No. 1, 01.01.1996, p. 137-143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of simvastatin on plasma lipids and apolipoproteins in familial hypercholesterolemic swine

AU - Hasler-Rapacz, Judith

AU - Kempen, Herman J.

AU - Princen, Hans M.G.

AU - Kudchodkar, Bhalchandra J.

AU - Lacko, Andras G.

AU - Rapacz, Jan

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG). LDL-cholesterol (LDL- C), apolipoproteins (apo) B, CIII, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals exhibiting TC≥250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL- C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25%). LDL-C (-27%), lathosterol (-40%), apoB (- 22%), apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (-12%) and apoA-I (-11%) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoa- I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC. LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swines is similar to that observed in humans, although the drug is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.

AB - Familial hypercholesterolemia (FHC) in swine, which resembles human familial combined hyperlipidemia, is a complex lipid and lipoprotein disorder associated with the development of severe coronary lesions similar to those occurring in advanced human coronary disease. The disorder is characterized by elevated plasma total cholesterol (TC), triglycerides (TG). LDL-cholesterol (LDL- C), apolipoproteins (apo) B, CIII, and E, and by decreased levels of HDL-cholesterol (HDL-C), apoA-I, and lecithin:cholesterol acyltransferase (LCAT) activity. A dose-response study with simvastatin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was conducted in four treatment groups of FHC animals exhibiting TC≥250 mg/dL. The animals were fed 0, 80, 200, or 400 mg simvastatin daily for 3 weeks. The measured serum parameters included the levels of TC, VLDL-C, LDL- C, HDL-C, TG, lathosterol, apoA-I, B, C-III, and E, as well as LCAT activity. Simvastatin at 200 mg/d significantly decreased the levels of TC (-25%). LDL-C (-27%), lathosterol (-40%), apoB (- 22%), apoC-III (-37%), and apoE (-24%) and modestly decreased the levels of HDL-C (-12%) and apoA-I (-11%) (percent relative to the average pretreatment and posttreatment baseline values) but did not affect the levels of TG, VLDL-C, the lathosterol/TC ratio, or LCAT activity. The levels of TC, LDL-C, apoB, and E were also lowered by simvastatin at 80 or 400 mg/d, but to a lesser extent than at 200 mg/d, while the other parameters were not influenced at these doses. The simvastatin-induced decreases of LDL-C, HDL-C, and apoa- I, B, C-III, and E were significantly correlated among each other. These results show that the trend of responses in TC. LDL-C, apoB, apoC-III, and apoE to simvastatin in the FHC swines is similar to that observed in humans, although the drug is less potent and efficacious in swine, while the results are different from those in humans with regard to the remaining parameters.

KW - animal model

KW - apolipoproteins

KW - familial hypercholesterolemia

KW - simvastatin

KW - swine

UR - http://www.scopus.com/inward/record.url?scp=0030053144&partnerID=8YFLogxK

U2 - 10.1161/01.ATV.16.1.137

DO - 10.1161/01.ATV.16.1.137

M3 - Article

C2 - 8548414

AN - SCOPUS:0030053144

VL - 16

SP - 137

EP - 143

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 1

ER -