To determine whether production or catabolism of low density lipoprotein (LDL) is the major factor controlling LDL concentrations in subjects with plasma cholesterol levels from low-normal to mildly elevated, measurements of apoprotein of LDL (apoLDL) turnover were performed in 16 patients with various plasma cholesterol concentrations. Cholesterol balance studies were done simultaneously in 13 of these patients. Plasma concentrations of apoLDL and LDL-cholesterol were positively correlated with synthetic rates of apoLDL (r = 0.74, P less than 0.001; r = 0.50, P less than 0.05, respectively). No correlation was noted between the fractional catabolic rate for apoLDL and apoLDL levels (or LDL-cholesterol). For further analysis, the patients were divided into three groups with stepwise increases in apoLDL concentrations. When apoLDL levels rose significantly, from 83 +/- 5 SEM to 122 +/- 2 to 149 +/- 5 mg/dl, synthetic rates for apoLDL also increased significantly from 11.6 +/- 12. to 17.0 +/- 0.9 to 23.8 +/- 1.8 mg/d/kg ideal weight. In contrast, the fractional catabolic rate of apoLDL was not different among the three groups (0.32 +/- 0.03 vs. 0.29 +/- 0.02 vs. 0.33 +/- 0.03/d). No relation was noted between synthesis of total body cholesterol (or bile acids) and concentrations, production rates, or removal of apoLDL. Thus, concentrations of apoLDL and LDL-cholesterol in these subjects with plasma cholesterol levels from low-normal to mildly elevated were regulated mainly by synthetic rates of apoLDL and not by LDL catabolism.
Y A Kesaniemi, S M Grundy
Title and authors | Publication | Year |
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Population pharmacokinetic and pharmacokinetic-pharmacodynamic modeling of bempedoic acid and low-density lipoprotein cholesterol in healthy subjects and patients with dyslipidemia.
Jadhav SB, Amore BM, Bockbrader H, Crass RL, Chapel S, Sasiela WJ, Emery MG |
Journal of Pharmacokinetics and Pharmacodynamics | 2023 |
Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose-response model.
Jadhav SB, Crass RL, Chapel S, Kerschnitzki M, Sasiela WJ, Emery MG, Amore BM, Barrett PHR, Watts GF, Catapano AL |
2022 | |
Pharmacodynamic effect of bempedoic acid and statin combinations: predictions from a dose–response model
SB Jadhav, RL Crass, S Chapel, M Kerschnitzki, WJ Sasiela, MG Emery, BM Amore, PH Barrett, GF Watts, AL Catapano |
European Heart Journal - Cardiovascular Pharmacotherapy | 2021 |
The Severe Hypercholesterolemia Phenotype
AD Sniderman, S Tsimikas, S Fazio |
Journal of the American College of Cardiology | 2014 |
Regulation of plasma LDL: the apoB paradigm
AD Sniderman, JD Graaf, P Couture, K Williams, RS Kiss, GF Watts |
Clinical Science | 2009 |
Low-density lipoprotein clearance in patients with chronic renal failure
H Kastarinen, S Horkko, H Kauma, A Karjalainen, MJ Savolainen, YA Kesaniemi |
Nephrology Dialysis Transplantation | 2009 |
Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption
JJ Repa, SD Turley, G Quan, JM Dietschy |
Journal of lipid research | 2005 |
Influence of an asparagine to lysine mutation at amino acid 3516 of apolipoprotein B on low-density lipoprotein receptor binding
D Gaffney, CR Pullinger, DS O'Reilly, MS Hoffs, I Cameron, JK Vass, MV Kulkarni, JP Kane, VN Schumaker, GF Watts, CJ Packard |
Clinica Chimica Acta | 2002 |
Fatty acids differentially regulate hepatic cholesteryl ester formation and incorporation into lipoproteins in the liver of the mouse
C Xie, LA Woollett, SD Turley, JM Dietschy |
Journal of lipid research | 2002 |
Governance of the concentration of plasma LDL: a reevaluation of the LDL receptor paradigm
A D Sniderman, X J Zhang, K Cianflone |
Atherosclerosis | 2000 |
Mechanisms Regulating LDL Metabolism in Subjects on Peroral and Transdermal Estrogen Replacement Therapy
A Karjalainen, J Heikkinen, MJ Savolainen, AC Bäckström, YA Kesäniemi |
Arteriosclerosis, thrombosis, and vascular biology | 2000 |
Variation of apolipoprotein B as a possible cause of decreased low density lipoprotein clearance and hypercholesterolemia
T Korhonen, MJ Savolainen, YA Kesäniemi |
Atherosclerosis | 1999 |
Evidence of circadian rhythm in low-density lipoprotein apoB catabolism and its impact on the estimation of kinetic parameters
Werynski, Nahorski, Berglund, Ericsson, Angelin, Eriksson |
European Journal of Clinical Investigation | 1999 |
Identification of a metabolic difference accounting for the hyper- and hyporesponder phenotypes of cynomolgus monkey
SD Turley, DK Spady, JM Dietschy |
Journal of lipid research | 1997 |
Binding affinity and particle size of LDL in subjects with moderate hypercholesterolemia: relationship with in vivo LDL metabolism
K Yamane, S Kataoka, NA Le, M Paidi, WJ Howard, JS Hannah, BV Howard |
Journal of lipid research | 1996 |
Relationships of plasma and hepatic variables with rates of plasma low-density lipoprotein apolipoprotein B metabolism in baboons fed low- and high-fat diets
RS Kushwaha, PH Barrett, CA Reardon, DS Lewis, KD Carey, GS Getz, HC McGill |
Metabolism | 1995 |
Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism
K Kervinen, S Hörkkö, WF Beltz, YA Kesaniemi |
Alcohol | 1995 |
Overproduction of small very low density lipoproteins (Sf 20-60) in moderate hypercholesterolemia: relationships between apolipoprotein B kinetics and plasma lipoproteins
A Gaw, CJ Packard, GM Lindsay, BA Griffin, MJ Caslake, AR Lorimer, J Shepherd |
Journal of lipid research | 1995 |
Regulation of serum cholesterol level in middle-aged and elderly men. Relation of cholesterol absorption and synthesis to lipoprotein metabolism
H Gylling, T Strandberg, R Tilvis, TA Miettinen |
Arteriosclerosis Thrombosis and Vascular Biology | 1994 |
Deletion of exon 15 of the LDL receptor gene is associated with a mild form of familial hypercholesterolemia. FH-Espoo
PV Koivisto, UM Koivisto, PT Kovanen, H Gylling, TA Miettinen, K Kontula |
Arteriosclerosis Thrombosis and Vascular Biology | 1993 |
Lovastatin enhances hepatic uptake of low density lipoprotein in humans
K Kervinen, MJ Savolainen, JI Heikkilä, YA Kesäniemi |
Journal of lipid research | 1993 |
Metabolism of plasma low density lipoproteins in familial combined hyperlipidaemia: effect of acipimox therapy
S Ericsson, M Eriksson, L Berglund, B Angelin |
Journal of Internal Medicine | 1992 |
Carbamylation-induced alterations in low-density lipoprotein metabolism
S Hörkkö, MJ Savolainen, K Kervinen, YA Kesäniemi |
Kidney International | 1992 |
Influence of gender, body mass index, and age on response of plasma lipids to dietary fat plus cholesterol
PM Clifton, PJ Nestel |
Arteriosclerosis Thrombosis and Vascular Biology | 1992 |
Influence of age on the metabolism of plasma low density lipoproteins in healthy males
S Ericsson, M Eriksson, S Vitols, K Einarsson, L Berglund, B Angelin |
Journal of Clinical Investigation | 1991 |
Increased removal of remnants of triglyceride-rich lipoproteins on a diet rich in polyunsaturated fatty acids
PN Demacker, IG Reijnen, MB Katan, PM Stuyt, AF Stalenhoef |
European Journal of Clinical Investigation | 1991 |
Atherosclerotic Plaques
RW Wissler, MG Bond, M Mercuri, P Tanganelli, G Weber, G Friedman |
1991 | |
Clinical Value of Apolipoprotein Measurement
D Bhatnagar, PN Durrington |
Annals of Clinical Biochemistry | 1991 |
Analysis of low density lipoprotein apheresis: post-treatment rebound using mathematical models
A Werynski, PS Malchesky, H Nomura, Y Nose |
Computer Methods and Programs in Biomedicine | 1990 |
Effects of estrogen on low density lipoprotein metabolism in males. Short-term and long-term studies during hormonal treatment of prostatic carcinoma
M Eriksson, L Berglund, M Rudling, P Henriksson, B Angelin |
Journal of Clinical Investigation | 1989 |
Estimation of turnover of low density lipoproteins by simplified methods
GL Vega, SM Grundy |
Atherosclerosis | 1989 |
Kinetik der Lipide und Lipoproteine mit Bestimmung der Recovery-Rate im Non Steady State nach Plasma-, Membranfiltrations- und Dextransulfatadsorptionsapherese bei Hypercholesterinämie - Kinetics of Lipids and Lipoproteins with Determination of Recovery Rates in non-steady state after Plasma-, Membranefiltration and Dextransulfate Adsorption Apheresis for Hypercholesterolemia
W Schwartzkopff, H Gräfenhahn, A Nold, H Baeyer, A Bimmermann, J Schleicher |
Biomedizinische Technik/Biomedical Engineering | 1989 |
HYPOCHOLESTEROLAEMIA AND INCREASED ELIMINATION OF LOW-DENSITY LIPOPROTEINS IN METASTATIC CANCER OF THE PROSTATE
P Henriksson, S Ericsson, R Stege, M Eriksson, M Rudling, L Berglund, B Angelin |
The Lancet | 1989 |
Bile acid-lipoprotein interactions: Effects of ursodeoxycholic acid (ursodiol)
H Fromm |
Digestive Diseases and Sciences | 1989 |
Studies on the Expression of Genes Encoding Apolipoproteins B100 and B48 and the Low Density Lipoprotein Receptor in Nonhuman Primates
M Sorci-Thomas, MD Wilson, FL Johnson, DL Williams, LL Rudel |
The Journal of biological chemistry | 1989 |
Interaction of aging and dietary fat in the regulation of low density lipoprotein transport in the hamster
DK Spady, JM Dietschy |
Journal of lipid research | 1989 |
Modelling of LDL-apheresis: System efficacy and rebound kinetics
F Kochinke, H Baeyer, I Schwaner, H Gräfenhahn, A Nold, R Schwerdtfeger, W Schwartzkopff |
Plasma Therapy and Transfusion Technology | 1988 |
Multicentric reticulohistiocytosis, another lipid disorder with normolipidemic xanthomatosis?
YA Kesäniemi, C Ehnholm, TA Miettinen |
Atherosclerosis | 1987 |
Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis
CM Ballantyne, GL Vega, C East, G Richards, SM Grundy |
Metabolism | 1987 |
Regulation of low-density lipoprotein apolipoprotein B levels
YA Kesäniemi, M Färkkilä, K Kervinen, P Koivisto, M Vuoristo, TA Miettinen |
American Heart Journal | 1987 |
Cholesterol metabolism and aging
RA Kreisberg, S Kasim |
The American Journal of Medicine | 1987 |
Atherosclerosis and Cardiovascular Diseases
S Lenzi, GC Descovich |
1987 | |
Modulation of low density lipoprotein receptor activity by bile acids: differential effects of chenodeoxycholic and ursodeoxycholic acids in the hamster
M Malavolti, H Fromm, S Ceryak, IM Roberts |
Journal of lipid research | 1987 |
Metabolic basis of hyperapobetalipoproteinemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia
B Teng, AD Sniderman, AK Soutar, GR Thompson |
Journal of Clinical Investigation | 1986 |
Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo
HN Ginsberg, NA Le, IJ Goldberg, JC Gibson, A Rubinstein, P Wang-Iverson, R Norum, WV Brown |
Journal of Clinical Investigation | 1986 |
The evaluation and treatment of hypercholesterolemia in primary care practice
WL Peters, AH Goroll |
Journal of General Internal Medicine | 1986 |
Genetic and cultural inheritance of serum lipids, low and high density lipoprotein cholesterol and serum apolipoproteins A-I, A-II and B
A Hamsten, L Iselius, G Dahlén, U Faire |
Atherosclerosis | 1986 |
Regulation of plasma levels of low-density lipoprotein cholesterol: interpretation of data on low-density lipoprotein turnover in man
JB Meddings, JM Dietschy |
Circulation | 1986 |
Regulation of the production and catabolism of plasma low density lipoproteins in hypertriglyceridemic subjects. Effect of weight loss
HN Ginsberg, NA Le, JC Gibson |
Journal of Clinical Investigation | 1985 |
Comparisons of metabolism of apolipoprotein B in normal subjects, obese patients, and patients with coronary heart disease
YA Kesäniemi, WF Beltz, SM Grundy |
Journal of Clinical Investigation | 1985 |
Abnormalities in Metabolism of Low Density Lipoproteins Associated with Coronary Heart Disease
SM Grundy, GL Vega, YA Kesäniemi |
Acta Medica Scandinavica | 1985 |
Lipids, Nutrition, and Coronary Heart Disease
WL Peters, DM Hegsted, A Leaf |
Cardiology Clinics | 1985 |
Kinetic mechanisms determining variability in low density lipoprotein levels and rise with age
SM Grundy, GL Vega, DW Bilheimer |
Arteriosclerosis (Dallas, Tex.) | 1985 |
Influence of mevinolin on metabolism of low density lipoproteins in primary moderate hypercholesterolemia
SM Grundy, GL Vega |
Journal of lipid research | 1985 |
Low density lipoprotein metabolism in hypertriglyceridemic and normolipidemic patients with coronary heart disease
GL Vega, WF Beltz, SM Grundy |
Journal of lipid research | 1985 |
WHY DOES PLASMA LOW DENSITY LIPOPROTEIN CONCENTRATION IN ADULTS INCREASE WITH AGE?
NE Miller |
The Lancet | 1984 |
Isolation and analysis of lipoproteins secreted by rat liver hepatocytes
DE Vance, DB Weinstein, D Steinberg |
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | 1984 |
Turnover of low density lipoproteins during inhibition of cholesterol absorption by neomycin
YA Kesäniemi, SM Grundy |
Arteriosclerosis (Dallas, Tex.) | 1984 |
Influence of probucol on cholesterol and lipoprotein metabolism in man
YA Kesäniemi, SM Grundy |
Journal of lipid research | 1984 |
Receptor-mediated catabolism of low density lipoprotein in man. Quantitation using glucosylated low density lipoprotein
YA Kesaniemi, JL Witztum, UP Steinbrecher |
Journal of Clinical Investigation | 1983 |
Studies on the production of low density lipoproteins by perfused livers from nonhuman primates. Effect of dietary cholesterol
FL Johnson, RW st Clair, LL Rudel |
Journal of Clinical Investigation | 1983 |
Atherosclerosis and apoproteins B and A-I
PO Kwiterovich, AD Sniderman |
Preventive Medicine | 1983 |
Normocholesterolemic tendon xanthomatosis with overproduction of apolipoprotein B
GL Vega, DR Illingworth, SM Grundy, FT Lindgren, WE Connor |
Metabolism | 1983 |
Atherosclerosis: Pathology, pathogenesis, and role of risk factors
SM Grundy |
Disease-a-Month | 1983 |
Increased low density lipoprotein production associated with obesity
YA Kesaniemi, SM Grundy |
Arteriosclerosis (Dallas, Tex.) | 1983 |
Overproduction of low density lipoproteins associated with coronary heart disease
YA Kesaniemi, SM Grundy |
Arteriosclerosis (Dallas, Tex.) | 1983 |
Atherosclerosis VI
FG Schettler, AM Gotto, G Middelhoff, AJ Habenicht, KR Jurutka |
1983 | |
Low density lipoprotein metabolism in the normal to moderately elevated range of plasma cholesterol: comparisons with familial hypercholesterolemia
LA Simons, S Balasubramaniam, J Holland |
Journal of lipid research | 1983 |
Advances in Lipid Research
AM Scanu |
Advances in Lipid Research | 1965 |