Abstract
Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism is that inhibition of cholesterol synthesis interferes with the assembly of VLDL particles. Since one molecule of apolipoprotein (apo) B is required for the proper assembly and secretion of each VLDL and secretion of apo B may be regulated by various lipid components of the lipoproteins, question arises whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To address this issue, we investigated the effect of lovastatin on the secretion rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day × 13 days), as compared with placebo, decreased the concentrations of fasting plasma triglyceride (1740 ± 170 vs. 3130 ± 790 μg/ml) and VLDL-triglyceride (1379 ± 59 vs. 3082 ± 715 μg/ml). There was a small but non-significant decrease in VLDL-apo B (19 ± 2 μg/ml vs. 26 ± 7 μg/ml). Thus, lovastatin significantly decreased the ratio of triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group). Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous injection of Triton WR-1339. Lovastatin, as compared with placebo, decreased the secretion rates of plasma triglyceride (78 vs. 123 μg/ml per min) and VLDL-triglyceride (102 vs. 167 μg/ml per min) significantly, but not of VLDL-phospholipid (11 vs. 14 μg/ml per min), VLDL-free cholesterol (5.3 vs. 6.6 μg/ml per min) or VLDL-apo B (1.1 vs. 1.0 μg/ml per min). Consequently, newly-secreted VLDL particles had a significantly smaller ratio of triglyceride to apo B (91 vs. 184) and smaller estimated particle sizes (46 + 2.4 nm vs. 58 + 2.6 nm in diameter). In summary, the present study demonstrated that, in the hypertriglyceridemic state, lovastatin interfered with the secretion of VLDL-triglyceride but not of VLDL-apo B, resulting in the production of smaller, triglyceride-depleted VLDL particles.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 147-152 |
| Number of pages | 6 |
| Journal | Atherosclerosis |
| Volume | 104 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - 1993 |
| Externally published | Yes |
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Keywords
- HMG-CoA reductase inhibitors
- VLDL-apo B
- VLDL-composition
- Zucker fa/fa rat
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Effect of lovastatin on the secretion of very low density lipoprotein lipids and apolipoprotein B in the hypertriglyceridemic Zucker obese rat. / Karakas, Siddika E; Elovson, John; Khilnani, Sheila; Almario, Rogelio U.; Catherine Jen, K. L.
In: Atherosclerosis, Vol. 104, No. 1-2, 1993, p. 147-152.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of lovastatin on the secretion of very low density lipoprotein lipids and apolipoprotein B in the hypertriglyceridemic Zucker obese rat
AU - Karakas, Siddika E
AU - Elovson, John
AU - Khilnani, Sheila
AU - Almario, Rogelio U.
AU - Catherine Jen, K. L.
PY - 1993
Y1 - 1993
N2 - Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism is that inhibition of cholesterol synthesis interferes with the assembly of VLDL particles. Since one molecule of apolipoprotein (apo) B is required for the proper assembly and secretion of each VLDL and secretion of apo B may be regulated by various lipid components of the lipoproteins, question arises whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To address this issue, we investigated the effect of lovastatin on the secretion rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day × 13 days), as compared with placebo, decreased the concentrations of fasting plasma triglyceride (1740 ± 170 vs. 3130 ± 790 μg/ml) and VLDL-triglyceride (1379 ± 59 vs. 3082 ± 715 μg/ml). There was a small but non-significant decrease in VLDL-apo B (19 ± 2 μg/ml vs. 26 ± 7 μg/ml). Thus, lovastatin significantly decreased the ratio of triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group). Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous injection of Triton WR-1339. Lovastatin, as compared with placebo, decreased the secretion rates of plasma triglyceride (78 vs. 123 μg/ml per min) and VLDL-triglyceride (102 vs. 167 μg/ml per min) significantly, but not of VLDL-phospholipid (11 vs. 14 μg/ml per min), VLDL-free cholesterol (5.3 vs. 6.6 μg/ml per min) or VLDL-apo B (1.1 vs. 1.0 μg/ml per min). Consequently, newly-secreted VLDL particles had a significantly smaller ratio of triglyceride to apo B (91 vs. 184) and smaller estimated particle sizes (46 + 2.4 nm vs. 58 + 2.6 nm in diameter). In summary, the present study demonstrated that, in the hypertriglyceridemic state, lovastatin interfered with the secretion of VLDL-triglyceride but not of VLDL-apo B, resulting in the production of smaller, triglyceride-depleted VLDL particles.
AB - Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism is that inhibition of cholesterol synthesis interferes with the assembly of VLDL particles. Since one molecule of apolipoprotein (apo) B is required for the proper assembly and secretion of each VLDL and secretion of apo B may be regulated by various lipid components of the lipoproteins, question arises whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To address this issue, we investigated the effect of lovastatin on the secretion rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day × 13 days), as compared with placebo, decreased the concentrations of fasting plasma triglyceride (1740 ± 170 vs. 3130 ± 790 μg/ml) and VLDL-triglyceride (1379 ± 59 vs. 3082 ± 715 μg/ml). There was a small but non-significant decrease in VLDL-apo B (19 ± 2 μg/ml vs. 26 ± 7 μg/ml). Thus, lovastatin significantly decreased the ratio of triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group). Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous injection of Triton WR-1339. Lovastatin, as compared with placebo, decreased the secretion rates of plasma triglyceride (78 vs. 123 μg/ml per min) and VLDL-triglyceride (102 vs. 167 μg/ml per min) significantly, but not of VLDL-phospholipid (11 vs. 14 μg/ml per min), VLDL-free cholesterol (5.3 vs. 6.6 μg/ml per min) or VLDL-apo B (1.1 vs. 1.0 μg/ml per min). Consequently, newly-secreted VLDL particles had a significantly smaller ratio of triglyceride to apo B (91 vs. 184) and smaller estimated particle sizes (46 + 2.4 nm vs. 58 + 2.6 nm in diameter). In summary, the present study demonstrated that, in the hypertriglyceridemic state, lovastatin interfered with the secretion of VLDL-triglyceride but not of VLDL-apo B, resulting in the production of smaller, triglyceride-depleted VLDL particles.
KW - HMG-CoA reductase inhibitors
KW - VLDL-apo B
KW - VLDL-composition
KW - Zucker fa/fa rat
UR - http://www.scopus.com/inward/record.url?scp=0027732505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027732505&partnerID=8YFLogxK
U2 - 10.1016/0021-9150(93)90185-W
DO - 10.1016/0021-9150(93)90185-W
M3 - Article
C2 - 8141838
AN - SCOPUS:0027732505
VL - 104
SP - 147
EP - 152
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 1-2
ER -