New lipid lowering drugs and new effects of old drugs

Dujovne, Carlos A.

doi:10.1097/00041433-199712000-00007

Cited by 36 publications

(15 citation statements)

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“…Pravastatin and FLU are hydrophilic statins (Dujovne 1997). Their dosage did not influence the content of lipid classes to such extent as the li-pophilic LOV.…”

Section: Discussionmentioning

confidence: 91%

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Vecka

Tvrzická

Staňková

et al. 2004

Tohoku J. Exp. Med.

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Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic beneficial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the rat brain tissue. Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravastatin, fluvastatin or placebo (control) once daily for six weeks. In rats treated with lovastatin or pravastatin, decreased cholesterol and increased ceramide monohexoside contents in the brain tissue were observed in comparison with control. Treatment with fluvastatin or lovastatin resulted in increased sphingomyelin and decreased diphosphatidylglycerol contents. The most important changes in the fatty acid profile were observed in ceramide monohexosides; treatment with fluvastatin decreased the content of saturated and increased the content of polyunsaturated fatty acids. Fenofibrate treatment led to decreased content of saturated fatty acids in phosphatidylethanolamines. In conclusion, statin treatment resulted in the decreased content of cholesterol and diphosphatidylglycerol associated with the increased content of sphingolipids in the rat brain tissue. As cholesterol and sphingolipids are important components of brain membranes, the observed alterations in the composition brain lipids might be involved in genesis of neurological and mental symptoms following statin therapy.statin; fibrate; brain; lipids; fatty acid

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“…Pravastatin and FLU are hydrophilic statins (Dujovne 1997). Their dosage did not influence the content of lipid classes to such extent as the li-pophilic LOV.…”

Section: Discussionmentioning

confidence: 91%

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Vecka

Tvrzická

Staňková

et al. 2004

Tohoku J. Exp. Med.

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“…Pravastatin significantly lowered serum and LDL cholesterol levels by 20% and 24%, respectively, as expected. 53 This may be mediated by a reduced assembly and secretion of very low-density lipoprotein apolipoprotein B100 21,54 as well as an enhanced turnover of hepatic LDL receptors. 20 As a consequence, a diminished hepatic secretion of very low-density lipoprotein cholesterol into and an enhanced uptake of intermediate-density lipoprotein cholesterol and LDL cholesterol from plasma into liver, intestinal or other extrahepatic 55 tissues may occur.…”

Section: Discussionmentioning

confidence: 99%

The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans

et al. 1999

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3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to suppress biliary cholesterol secretion and saturation. It remains unproven whether this is mediated by inhibition of cholesterol synthesis. Therefore, the effect of a long-term administration of pravastatin on cholesterogenesis and on biliary lipid secretion was investigated in seven healthy volunteers. Placebo or 40 mg of pravastatin were taken daily at bedtime for 5 weeks using a double-blind crossover design. During the last week, 12 hours after the last drug intake 0.04 mmol [1-13 C]acetate/kg · h and 0.5 g polyethylene glycol 4,000/h were infused intraduodenally for 15 hours. Plasma and duodenal bile samples were collected hourly. Thereafter, the decay of [ 13 C]labeled plasma cholesterol was measured during the following 3 days. The fractional and absolute syntheses of plasma and biliary cholesterol were determined by gas chromatography mass spectrometry using mass isotopomer distribution analysis. At the end of the pravastatin period plasma total and low-density lipoprotein (LDL) cholesterol had decreased by 20% and 24%, respectively. Similarly, pravastatin suppressed biliary secretion rates of cholesterol, total bile acids and phospholipids (P F .05) by 46%, 36%, and 51%. As a consequence, cholesterol saturation index remained unchanged. However, fractional syntheses of cholesterol were comparable (P G .05) on placebo compared with pravastatin with 3.1% versus 4.0% in plasma and 4.3% versus 5.2% in bile after 15 hours, respectively. The mean absolute synthesis rates amounted to 0.3 mg/kg/h on placebo versus 0.4 on pravastatin (P G .05). In conclusion, the pravastatin-induced reduction of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis. (HEPATOLOGY 1999;30:14-20.)A variety of defects are realized to explain the pathogenesis of cholesterol gallstone formation, including cholesterol supersaturation as well as gallbladder hypomotility, rapid nucleation, and a mucin hypersecretion. Most likely a sustained cholesterol supersaturation of bile 1 owing to hepatic hypersecretion of cholesterol 2 stands at the beginning of this process. In animal studies the origin of biliary secreted cholesterol has been well defined. In rats and hamsters the amount of newly synthesized cholesterol secreted into bile amounts to 8% to 18% and 2% to 5%, respectively. [3][4][5][6] In humans, most of the indirect evidence using standard radioisotope kinetics supported that 20% of biliary cholesterol were derived from de novo synthesis, 7 the majority being preformed cholesterol supplied by high-density lipoprotein cholesterol. 8 We have recently shown that the mass isotopomer distribution analysis (MIDA) technique allows for the direct measurement of the 4% to 5% of newly synthesized cholesterol formed from [ 13 C]acetate in bile and also that a significantly higher proportion of de novo cholesterol is secreted into bile as opposed to plasma in healthy individuals' circulation. 9 Thus, it seems tha...

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“…60 Other patients may be treated not only with statins but also with niacin, fibrates, and a resin (or ezetimibe) or newer agents such as cholesteryl ester transfer protein inhibitors and agents that raise high-density lipoprotein. [61][62][63][64] Administration of high-density lipoprotein cholesterol or apolipoprotein (Apo) A-I Milano are other potentially promising approaches toward stabilizing vulnerable plaques. Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression and stabilization of atherosclerotic plaques in animal models.…”

Section: Treatmentmentioning

confidence: 99%

Finding Vulnerable Atherosclerotic Plaques

Madjid

Zarrabi

Litovsky

et al. 2004

ATVB

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Previous Brief Review in this Series:• Choudhury RP, Fuster V, Badimon JJ. Fisher EA, Fayad ZA. MRI and characterization of atherosclerotic plaque: emerging appliations and molecular imaging. 2002;22:1065-1074.• Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. 2003;23:168 -175.• Oliver JJ, Webb DJ. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. 2003;23:554 -566. Finding Vulnerable Atherosclerotic Plaques Is It Worth the Effort?Mohammad Madjid, Alireza Zarrabi, Silvio Litovsky, James T. Willerson, Ward Casscells Abstract-Techniques to identify and treat vulnerable plaques are the focus of enormous research. Some have questioned the benefit of locating individual vulnerable plaque in a multifocal disease. On autopsy, it is found that most deaths are caused by thrombotic occlusion of a single plaque; simultaneous occurrence of 2 occlusive thrombi is rare, but a second vulnerable plaque is common, particularly in acute myocardial infarction (MI). Angiographic progression is poorly predicted by risk factors, and angiographic progression is a weak predictor of MI or death. Intravascular ultrasonography (intravascular ultrasound [IVUS]) studies find plaque rupture in most MI patients and in approximately half with unstable angina, but in only a minority of patients with stable angina. IVUS identifies a second vulnerable plaque in many patients with unstable angina, and in most MI patients. Angioscopy reveals a very low incidence of a second vulnerable plaque compared with angiography and IVUS, but identifies additional yellow plaques in many patients with stable angina and in most patients with unstable angina or MI. Using thermography catheters and a temperature cutoff of 0.1°C, approximately half the patients with stable angina have Ͼ1 hot lesion; however, if the cutoff is 0.2°C, only Ϸ15% have a second hot lesion. New imaging techniques may detect additional characteristics of plaques and new predictive models may assess the risk of vulnerable plaques and patients. This approach enables physicians to "buy time" by application of local therapies until systemic therapies stabilize plaques. This may also reduce the risk in subjects in whom systemic therapies do not work. tions of coronary heart disease, whereas superimpositions of thrombi over the plaques lead to acute coronary syndromes. To date, angiography has been the method of choice for detecting these problematic arterial lesions. However, this diagnostic technique, which approximately compares the degree of stenosis of arterial lesions relative to the proximal segments of the artery, does not provide insight into the disease state within the artery, and often fails to detect those lesions prone to thrombosis. A series of landmark angiographic studies in the mid 1980s demonstrated that nearly two-thirds of all MI originate at atherosclerotic lesions that lack hemodynamic significance. 2-6 Unfortunately, these "culprit" lesions, which have been termed vulnerable plaques, are undetectable...

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New lipid lowering drugs and new effects of old drugs

Cited by 36 publications

References 0 publications

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

The pravastatin-induced decrease of biliary cholesterol secretion is not directly related to an inhibition of cholesterol synthesis in humans

Finding Vulnerable Atherosclerotic Plaques

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