cerivastatin and mevastatin

Statins have apoptotic effects on many cell types. Hashimoto's thyroiditis (HT) is an autoimmune disease in which cell-mediated autoimmune mechanisms are pathogenetically involved.. The aim of this study was to evaluate the in vivo effects of Simvastatin on thyroid function, lymphocyte subtypes and also to investigate the apoptotic effects of Simvastatin, Mevastatin, Pravastatin and Cerivastatin on lymphocytes from patients with HT.. In the first part of the study, 11 patients with HT and subclinical hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks. Ten patients with SH and HT served as the control group. No treatment was given to controls. Thyroid function, C-reactive protein (CRP) levels and lymphocyte subtypes of both groups were determined before the study and after 8 weeks. In the second part of the study, the apoptotic effects of statins on lymphocytes were evaluated in patients with HT (n = 10) and normal subjects (n = 10) in vitro. Apoptosis was investigated by using Annexin-V and propidium iodide. Lymphocytes from patients and controls were incubated with different concentrations of Simvastatin, Cerivastatin, Mevastatin and Pravastatin.. An increase in serum free tri-iodothyronine and free thyroxine levels and a decrease in TSH levels were observed (P < 0.05) with Simvastatin treatment. CD4+ cells and B lymphocytes increased whilst CD8+ cells, natural killer cells and activated T lymphocytes decreased significantly in the treatment group (P < 0.05). The CRP level of the group also decreased with Simvastatin but it did not reach significance (P = 0.057). None of parameters was found to be different from the baseline in the control group. In in vitro experiments, apoptosis was observed in CD3 + (both in CD8+ and CD4+ cells) with all statins in both patient and control samples. Mevalonate, which was used in experiments, reversed apoptosis in some but not all samples.. The results of this study suggested that Simvastatin is an immune modulatory agent and improves thyroid function in patients with HT. This effect is probably mediated via lymphocyte apoptosis as demonstrated with in vitro experiments and is not confined to Simvastatin since Mevastatin, Pravastatin and Cerivastatin also induced apoptosis in lymphocytes.

Topics: Adult; Apoptosis; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; In Vitro Techniques; Lovastatin; Lymphocytes; Male; Middle Aged; Pravastatin; Pyridines; Simvastatin; Thyroid Gland; Thyroiditis, Autoimmune

Neural apoptosis-regulated convertase (NARC)-1 is the newest member of the proprotein convertase family implicated in the cleavage of a variety of protein precursors. The NARC-1 gene, PCSK9, has been identified recently as the third locus implicated in autosomal dominant hypercholesterolemia (ADH). The 2 other known genes implicated in ADH encode the low-density lipoprotein receptor and apolipoprotein B. As an approach toward the elucidation of the physiological role(s) of NARC-1, we studied its transcriptional regulation.. Using quantitative RT-PCR, we assessed NARC-1 regulation under conditions known to regulate genes involved in cholesterol metabolism in HepG2 cells and in human primary hepatocytes. We found that NARC-1 expression was strongly induced by statins in a dose-dependent manner and that this induction was efficiently reversed by mevalonate. NARC-1 mRNA level was increased by cholesterol depletion but insensitive to liver X receptor activation. Human, mouse, and rat PCSK9 promoters contain 2 typical conserved motifs for cholesterol regulation: a sterol regulatory element (SRE) and an Sp1 site.. PCSK9 regulation is typical of that of the genes implicated in lipoprotein metabolism. In vivo, PCSK9 is probably a target of SRE-binding protein (SREBP)-2.

Topics: Alitretinoin; Animals; Atorvastatin; Base Sequence; Cell Line; Cholesterol; Consensus Sequence; DNA-Binding Proteins; Gene Expression Regulation; Hepatocytes; Heptanoic Acids; Homeostasis; Humans; Hydroxycholesterols; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver X Receptors; Lovastatin; Mevalonic Acid; Mice; Orphan Nuclear Receptors; Promoter Regions, Genetic; Proprotein Convertase 9; Proprotein Convertases; Pyridines; Pyrroles; Quinolines; Rats; Receptors, Cytoplasmic and Nuclear; Regulatory Sequences, Nucleic Acid; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sequence Alignment; Sequence Homology, Nucleic Acid; Serine Endopeptidases; Simvastatin; Sp1 Transcription Factor; Species Specificity; Sterol Regulatory Element Binding Protein 2; Transcription Factors; Tretinoin