Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new mevacor research articles will be listed here shortly after becoming available to us.
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Medical research on mevacor
AMP-Activated Protein Kinase Promotes the Differentiation of Endothelial Progenitor Cells.
Arterioscler Thromb Vasc Biol. 2008 Jul 3;
Li X, Han Y, Pang W, Li C, Xie X, Shyy JY, Zhu Y
OBJECTIVE: Endothelial progenitor cells (EPCs) can differentiate into endothelial cells (ECs) and participate in postnatal vasculogenesis, but the mechanism of EPC differentiation remains largely unknown. We investigated the role of AMP-activated protein kinase (AMPK) in EPC differentiation and functions. METHODS AND RESULTS: Vascular endothelial growth factor caused the phosphorylation of AMPK, acetyl-coenzymeA (CoA) carboxylase (ACC), and eNOS in human cord blood-derived EPCs. The expression of EC markers, including VE-cadherin and intercellular adhesion molecule1 (ICAM-1), was also increased but blocked by Compound C, an AMPK inhibitor. AICAR, an AMPK agonist, increased the phosphorylation of ACC and eNOS and the expression of EC markers in a time- and dose-dependent manner, which reinforces the positive effect of AMPK on EPC differentiation. The effects of AICAR could be blocked by treatment with L-NAME, an eNOS inhibitor. Functionally, AICAR increased but Compound C decreased the angiogenesis of EPCs in vitro and in vivo. Furthermore, lovastatin promoted the activation of AMPK and eNOS, the expression of EC markers, tube formation, adhesion, and in vivo vasculogenesis of EPCs, which could be blocked by treatment with Compound C. CONCLUSIONS: The activation of eNOS by AMPK during EPC differentiation provides a novel mechanism for the pleiotropic effects of statins in benefiting the cardiovascular system.
Transdermal Lovastatin Enhances Fracture Repair in Rats.
J Bone Miner Res. 2008 Jul 2;
Gutierrez GE, Edwards J, Garrett I, Nyman J, McCluskey B, Rossini G, Flores A, Neidre D, Mundy G
Microabstract Local statins stimulate BMP2 transcription and enhance fracture repair. Since large oral doses are ineffective therapeutically because of first pass hepatic metabolism, we examined low dose transdermal lovastatin in a rat fracture model. Results showed accelerated fracture healing.
Lovastatin, but not pravastatin, limits in vitro infection due to Coxiella burnetii.
J Antimicrob Chemother. 2008 Jun 30;
Botelho-Nevers E, Espinosa L, Raoult D, Rolain JM
[Biosynthesis of simvastatin--a mini-review]
Sheng Wu Gong Cheng Xue Bao. 2008 Mar; 24(3): 349-54
Yang Z, Gan C
Simvastatin, a semisynthetic derivertive of lovastatin, is an important drug for the treatment of hypercholesteromia, and is traditionally prepared by direct alkylation of lovastatin. Chemical reaction conditons are very rigid, and the final product is difficult to purify, also the pressure of labor protection and environment protection is very high. Recently, with the devolpement in the research of lovastatin biosynthesis, more and more attention has been paid to simvastatin biosynthesis. This paper compared the chemical and biological routes in simvastatin production. Simvastatin could be produced by direct fermentation with combinational biosynthesis method, and could also be synthesized from monacolin J with acyltransferase LovD.
Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death.
Neurosci Lett. 2008 Aug 8; 440(3): 260-4
Lee JK, Won JS, Singh AK, Singh I
Statins are inhibitors of HMG-CoA reductase that have been recently recognized as anti-inflammatory and neuroprotective drugs. Herein, we investigated anti-excitotoxic and anti-seizure effects of statins by using kainic acid (KA)-rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. We observed that pre-treatment with Lipitor (atorvastatin) efficiently reduced KA-induced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In addition, we also observed that lovastatin treatment attenuated KA- or glutamate-induced excitotoxicity of cultured hippocampal neurons. These observations suggest a potential for use of statin treatment in modulation of seizures and other neurological diseases associated with excitotoxicity.
FEBS Lett. 2008 Jun 27;
Herrero-Martin G, López-Rivas A
Statins are inhibitors of the mevalonate synthesis pathway that induce apoptosis in tumor cells although the apoptotic mechanism activated by statins remains to be elucidated. We have examined the role of the mitochondria-operated pathway of apoptosis in the cell death induced by statins in breast tumor cells and its regulation by protein prenylation and ErbB2 overexpression. Lovastatin treatment down-regulates the expression of Bcl-2 and activates apoptosis through a mitochondria-operated, ErbB2- regulated mechanism. Apoptosis induced by statins is independent of their effects on cholesterol synthesis and involves protein prenylation. Our results indicate that prenylation of apoptosis-regulating proteins is a key event in the survival of breast tumor cells and this requirement could be circumvented in cells overexpressing the oncogene ErbB2.
RENAL NA-K-CL COTRANSPORTER ACTIVITY AND VASOPRESSIN-INDUCED TRAFFICKING ARE LIPID RAFT-DEPENDENT.
Am J Physiol Renal Physiol. 2008 Jun 25;
Welker P, Boehlick A, Mutig K, Salanova M, Kahl T, Schlueter H, Blottner D, Ponce-Coria J, Gamba G, Bachmann S
Apical bumetanide-sensitive Na(+)-K(-)-2Cl(-)-cotransporter (NKCC2), the kidney-specific member of a cation-chloride cotransporter superfamily, is an integral membrane protein responsible for the transepithelial reabsorption of NaCl. The role of NKCC2 is essential for renal volume regulation. Vasopressin (AVP) controls NKCC2 surface expression in cells of the thick ascending limb of the loop of Henle (TAL). We found that 40-70% of Triton X-100-insoluble NKCC2 was present in cholesterol-enriched lipid rafts (LR) in rat kidney and cultured TAL cells. The related Na(+)Cl(-)-cotransporter, NCC, from rat kidney was distributed in LR as well. NKCC2-containing LR were detected both intracellularly and in the plasma membrane. Bumetanide-sensitive transport of NKCC2 as analyzed by 86Rb+ influx in Xenopus laevis oocytes was markedly reduced by methyl-beta-cyclodextrin (MbetaCD)-induced cholesterol depletion. In TAL, short term AVP application induced apical vesicular trafficking along with a shift of NKCC2 from non-raft to LR fractions. In parallel, increased colocalization of NKCC2 with the LR ganglioside GM1 and their polar translocation were assessed by confocal analysis. Apical biotinylation showed twofold increases in NKCC2 surface expression. These effects were blunted by mevalonate-lovastatin/MbetaCD-induced cholesterol deprivation. Collectively, these findings demonstrate that a pool of NKCC2 distributes in rafts. Results are consistent with a model in which LR mediate polar insertion, activity, and AVP-induced trafficking of NKCC2 in the control of transepithelial NaCl transport. Key words: thick ascending limb, lipid raft, Xenopus oocyte, cholesterol depletion.
Cloning and Characterization of Monacolin K Biosynthetic Gene Cluster from Monascus pilosus.
J Agric Food Chem. 2008 Jun 26;
Chen YP, Tseng CP, Liaw LL, Wang CL, Chen IC, Wu WJ, Wu MD, Yuan GF
Monacolin K is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus, and it has the same structure as lovastatin, which is mainly produced by Aspergillus terreus. In the present study, a bacterial artificial chromosome (BAC) clone, mps01, was screened from the BAC library constructed from Monascus pilosus BCRC38072 genomic DNA. The putative monacolin K biosynthetic gene cluster was found within a 42 kb region in the mps01 clone. The deduced amino acid sequences encoded by the nine genes designated as mokA- mokI, which share over 54% similarity with the lovastatin biosynthetic gene cluster in A. terreus, were assumed to be involved in monacolin K biosynthesis. A gene disruption construct designed to replace the central part of mokA, a polyketide synthase gene, in wild-type M. pilosus BCRC38072 with a hygromycin B resistance gene through homologous recombination, resulted in a mokA-disrupted strain. The disruptant did not produce monacolin K, indicating that mokA encoded the PKS responsible for monacolin K biosynthesis in M. pilosus BCRC38072.
Lakartidningen. 2008 May 7-13; 105(19): 1408-9; discussion 1409
Eklund K, Grip L, Israelsson B, Levin LA, Lindahl B, Wallentin L
Ugeskr Laeger. 2008 Jun 23; 170(26-32): 2323-6
Keiding H, Hildebrandt P, Alemao E, Davies GM
INTRODUCTION: The purpose of this analysis is to evaluate the cost effectiveness of ezetemibe coadministration compared to a shift to higher doses of simvastatin or to a more potent statin. MATERIALS AND METHODS: The calculations are based on a Markov model in which a patient who does not attain the desired cholesterol outcome with simvastatin treatment is treated either with ezetemibe coadministration, or with increased simvastatin doses, or with a more potent statin. Calculations are conducted for a total of 72 different patient types followed over the remainder of their lives. RESULTS: Ezetemibe coadministration evaluated over the entire lifetime will be somewhat more expensive than simvastatin titration but must, however, be seen in relation to improved survival and increased quality of life. For the typical patient, treatment will be associated with costs of between DKK 50,000 and 100,000 per gained year of life, which cannot be deemed too expensive in relation to other interventions provided by the Health Authorities. For some patient types who receive treatment with a potent statin (atorvastatin), savings will also be possible here as well as an increase in life expectancy and quality of life. CONCLUSION: The results of the study indicate that ezetemibe coadministration is cost effective. The results are sustainable even with quite significant changes of the estimates used and taking into account uncertainties in the material and methods.