Flow cytometric assessment of effects of fluvastatin on low-density lipoprotein receptor activity in stimulated T-lymphocytes from patients with heterozygous familial hypercholesterolemia.
To test the effects of fluvastatin on low-density lipoprotein (LDL) receptor activity in patients with heterozygous familial hypercholesterolemia, the authors measured LDL receptor activity in stimulated T-lymphocytes prepared from 34 patients before and after treatment with 40 mg fluvastatin daily for 12 weeks. Maximally induced pretreatment LDL receptor activities did not correlate with pretreatment plasma cholesterol levels or with changes in plasma cholesterol levels during treatment, and there were no significant changes in LDL receptor activity during treatment. Barring methodological problems, two explanations are possible. Insofar that LDL receptor activity in lymphocytes reflects LDL receptor activity in the liver, the results suggest that the primary response to treatment with fluvastatin in heterozygous familial hypercholesterolemia (FH) patients is not enhanced LDL receptor activity. Alternatively, fluvastatin increases LDL receptor activity in hepatocytes but has little effect on receptor-dependent lipoprotein catabolism in extrahepatic tissues in vivo.
Raungaard
B
B
Department of Internal Medicine and Cardiology, Aarhus Amtssygehus University Hospital, Denmark.
Brorholt-Petersen
J U
JU
Jensen
H K
HK
Faergeman
O
O
D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002232:Carbocyanines / Q000737:chemistry; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D000077340:Fluvastatin; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007211:Indoles / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D011973:Receptors, LDL / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000911:Antibodies, Monoclonal; D000924:Anticholesteremic Agents; D002232:Carbocyanines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D014280:Triglycerides; C024286:3,3'-dioctadecylindocarbocyanine; D000077340:Fluvastatin; D002784:Cholesterol; D016650:Fluorescein-5-isothiocyanate