Qualitative Effect of Fenofibrate and Quantitative Effect of Atorvastatin on LDL Profile in Combined Hyperlipidemia with dense LDL

Winkler, Karl; Weltzien, P; Friedrich, I.; Schmitz, Helga; Hh, Nickell; Hauck, Philip; Mm, Hoffmann; Mw, Baumstark; Wieland, Heinrich; März, Winfried

doi:10.1055/s-2004-817970

Cited by 25 publications

(18 citation statements)

References 47 publications

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“…Consequently, nuclear receptors represent potential targets for drug development because small-molecular-weight compounds can act as agonists or antagonists to modulate their activities and hence alter disease progression. Indeed, the fibrate class of compounds has been used to modulate PPAR␣ activity and treat hypertriglyceridemia and hypercholesterolemia (37). Likewise, the thiazolidinedione class of compounds, which act on PPAR␥, represent a group of antidiabetic drugs, and tamoxifen is an antiestrogen compound used in the treatment of breast cancer (38,39).…”

Section: Discussionmentioning

confidence: 99%

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

Reese

Oropeza

McLachlan

2013

J Virol

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In the human hepatoma cell line HepG2, retinoic acid, clofibric acid, and bile acid treatment can only modestly increase hepatitis B virus (HBV) biosynthesis. Utilizing the human embryonic kidney cell line 293T, it was possible to demonstrate that the retinoid X receptor ␣ (RXR␣) plus its ligand can support viral biosynthesis independently of additional nuclear receptors. In addition, RXR␣/peroxisome proliferator-activated receptor ␣ (PPAR␣) and RXR␣/farnesoid X receptor ␣ (FXR␣) heterodimeric nuclear receptors can also mediate ligand-dependent HBV transcription and replication when activated by clofibric acid and bile acid, respectively, independently of a requirement for the ligand-dependent activation of RXR␣. These observations indicate that there are at least three possible modes of ligand-mediated activation of HBV transcription and replication existing within hepatocytes, suggesting that multiple independent mechanisms control viral production in the livers of infected individuals. Hepatitis B virus (HBV) infection is primarily restricted to hepatocytes in the liver. This restriction is believed to occur at two distinct levels (1). The receptor(s) involved in viral entry is presumably present only on hepatocytes and governs species specificity (2). In addition, viral biosynthesis is restricted in a tissueand cell-type-specific manner because HBV transcription is dependent on liver-enriched transcription factors (3, 4). A variety of nuclear receptors have been shown to regulate HBV pregenomic 3.5-kb RNA synthesis and hence viral replication (5-7). Three of these nuclear receptors, retinoid X receptor (RXR), peroxisome proliferator-activated receptor (PPAR), and farnesoid X receptor (FXR), are ligand-dependent transcription factors that are activated by retinoids, peroxisome proliferators, and bile acids, respectively (8, 9). Therefore, it is apparent that the ligands for these nuclear receptors might be critical determinants of viral biosynthesis under both normal and pathophysiological conditions within the livers of infected individuals (10, 11).As the ligand-activated heterodimeric nuclear receptors RXR␣/PPAR␣ and RXR␣/FXR␣ regulate HBV pregenomic RNA synthesis by the recruitment of coactivators, it was of interest to evaluate the relative contributions of the individual heterodimeric partners to the overall level of viral transcription and replication (5, 6, 12). Characterization of the relative roles of individual polypeptides in the transcriptional activity of various heterodimeric nuclear receptors has been evaluated (13-15). This approach indicated that one partner might play a dominant role in controlling promoter activity depending on the nuclear receptors involved (13-15). Therefore, it was of interest to evaluate the effects of retinoids, peroxisome proliferators, and bile acids, alone or in combination, on HBV transcription and replication.In the current study, it is demonstrated that retinoids can activate HBV biosynthesis utilizing both RXR␣-containing homodimers and heterodimers. Alternativ...

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Section: Discussionmentioning

confidence: 99%

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

Reese

Oropeza

McLachlan

2013

J Virol

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“…The direct effects of fenofibrate on LDL size and subclasses was tested in 16 different studies [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] ; treatment with fenofibrate was beneficial in all studies and only in two reports such benefit was partial 54,55 ( Table 1). These studies were performed in patients with different forms of dyslipidaemia, including hypercholesterolemia, hypertriglyceridaemia and combined hyperlipoproteinaemia 42,[44][45][46]48,50,51,54 .…”

Section: Fenofibratementioning

confidence: 99%

“…These studies were performed in patients with different forms of dyslipidaemia, including hypercholesterolemia, hypertriglyceridaemia and combined hyperlipoproteinaemia 42,[44][45][46]48,50,51,54 . Patients with type 2a lipoproteinaemia showed a clear beneficial effect in two studies 45,46 .…”

Section: Fenofibratementioning

confidence: 99%

The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates

Rizzo

Berneis²

2007

Current Medical Research and Opinion

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“…Although the reduction in low-density lipoprotein (LDL)-cholesterol by fibrates always remains marginal (5-15%) [108][109][110], in a study by Winkler et al [111], fenofibrate lowers atherogenic small dense LDL more effectively than atorvastatin. However, in general, fibrates seem to be particularly effective in patients for whom a disturbance of the triglyceride-HDL axis is the primary lipid disorder.…”

Section: Coronary Heart Diseasementioning

confidence: 99%

Lipid-lowering drugs

Pahan

2006

Cell. Mol. Life Sci.

198

140

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Although a change in life-style is often the method of first choice for lipid lowering, lipid-lowering drugs, in general, help to control elevated levels of different forms of lipids in patients with hyperlipidemia. While one group of drugs, statins, lowers cholesterol, the other group, fibrates, is known to take care of fatty acids and triglycerides. In addition, other drugs, such as ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also being considered to manage hyperlipidemia. As lipids are very critical for cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular abnormalities in the general population. However, a number of recent studies indicate that apart from their lipid-lowering activities, statins and fibrates exhibit multiple functions to modulate intracellular signaling pathways, inhibit inflammation, suppress the production of reactive oxygen species, and modulate T cell activity. Therefore, nowadays, these drugs are being considered as possible therapeutics for several forms of human disorders including cancer, autoimmunity, inflammation, and neurodegeneration. Here I discuss these applications in the light of newly discovered modes of action of these drugs.

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Qualitative Effect of Fenofibrate and Quantitative Effect of Atorvastatin on LDL Profile in Combined Hyperlipidemia with dense LDL

Cited by 25 publications

References 47 publications

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

Independent Activation of Hepatitis B Virus Biosynthesis by Retinoids, Peroxisome Proliferators, and Bile Acids

The clinical significance of the size of low-density-lipoproteins and the modulation of subclasses by fibrates

Lipid-lowering drugs

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