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Article: Modulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cells
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TitleModulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cells
 
AuthorsSeto, SW3
Au, ALS3
Lam, TY3
Chim, SSC3
Lee, SMY4
Wan, S3
Tjiu, DCS5 2
Shigemura, N3
Yim, APC3
Chan, SW5
Tsui, SKW3
Leung, GPH1
Kwan, YW6 3
 
Issue Date2007
 
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
CitationBritish Journal Of Pharmacology, 2007, v. 151 n. 7, p. 987-997 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.bjp.0707327
 
AbstractBackground and Purpose: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca 2+- activated K + (BK Ca) channels. Experimental Approaches: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK Ca channel gatings of porcine coronary artery smooth muscle cells were evaluated. Key Results: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 μM) (hydrophobic), but not simvastatin Na + (hydrophilic), inhibited the BK Ca channels with a minimal recovery upon washout. Isopimaric acid (10 μM)-mediated enhancement of the BK Ca amplitude was reversed by external simvastatin. Simvastatin Na + (10 μM, applied internally), markedly attenuated isopimaric acid (10 μM)-induced enhancement of the BK Ca amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 μM) and geranylgeranyl pyrophosphate (20 μM) only prevented simvastatin (1 and 3 μM)-induced responses. simvastatin (10 μM) caused a rottlerin (1 μM)-sensitive (cycloheximide (10 μM)-insensitive) increase of PKC-δ protein expression. Conclusions and Implications: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK Ca channels of the arterial smooth muscle cells through multiple intracellular pathways. © 2007 Nature Publishing Group All rights reserved.
 
ISSN0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
DOIhttp://dx.doi.org/10.1038/sj.bjp.0707327
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorSeto, SW
 
dc.contributor.authorAu, ALS
 
dc.contributor.authorLam, TY
 
dc.contributor.authorChim, SSC
 
dc.contributor.authorLee, SMY
 
dc.contributor.authorWan, S
 
dc.contributor.authorTjiu, DCS
 
dc.contributor.authorShigemura, N
 
dc.contributor.authorYim, APC
 
dc.contributor.authorChan, SW
 
dc.contributor.authorTsui, SKW
 
dc.contributor.authorLeung, GPH
 
dc.contributor.authorKwan, YW
 
dc.date.accessioned2012-10-30T06:13:34Z
 
dc.date.available2012-10-30T06:13:34Z
 
dc.date.issued2007
 
dc.description.abstractBackground and Purpose: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca 2+- activated K + (BK Ca) channels. Experimental Approaches: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK Ca channel gatings of porcine coronary artery smooth muscle cells were evaluated. Key Results: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 μM) (hydrophobic), but not simvastatin Na + (hydrophilic), inhibited the BK Ca channels with a minimal recovery upon washout. Isopimaric acid (10 μM)-mediated enhancement of the BK Ca amplitude was reversed by external simvastatin. Simvastatin Na + (10 μM, applied internally), markedly attenuated isopimaric acid (10 μM)-induced enhancement of the BK Ca amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 μM) and geranylgeranyl pyrophosphate (20 μM) only prevented simvastatin (1 and 3 μM)-induced responses. simvastatin (10 μM) caused a rottlerin (1 μM)-sensitive (cycloheximide (10 μM)-insensitive) increase of PKC-δ protein expression. Conclusions and Implications: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK Ca channels of the arterial smooth muscle cells through multiple intracellular pathways. © 2007 Nature Publishing Group All rights reserved.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationBritish Journal Of Pharmacology, 2007, v. 151 n. 7, p. 987-997 [How to Cite?]
DOI: http://dx.doi.org/10.1038/sj.bjp.0707327
 
dc.identifier.doihttp://dx.doi.org/10.1038/sj.bjp.0707327
 
dc.identifier.epage997
 
dc.identifier.hkuros157508
 
dc.identifier.issn0007-1188
2013 Impact Factor: 4.990
2013 SCImago Journal Rankings: 2.253
 
dc.identifier.issue7
 
dc.identifier.pmid17558433
 
dc.identifier.scopuseid_2-s2.0-34547602966
 
dc.identifier.spage987
 
dc.identifier.urihttp://hdl.handle.net/10722/171357
 
dc.identifier.volume151
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=0007-1188&site=1
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofBritish Journal of Pharmacology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAdult
 
dc.subject.meshAged
 
dc.subject.meshAnimals
 
dc.subject.meshBlotting, Western
 
dc.subject.meshCaveolin 1 - Biosynthesis
 
dc.subject.meshCell Line
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshCoronary Vessels - Cytology - Drug Effects - Physiology
 
dc.subject.meshDose-Response Relationship, Drug
 
dc.subject.meshEnzyme Activation - Drug Effects
 
dc.subject.meshFemale
 
dc.subject.meshHumans
 
dc.subject.meshHydroxymethylglutaryl-Coa Reductase Inhibitors - Pharmacology
 
dc.subject.meshImidazoles - Pharmacology
 
dc.subject.meshMale
 
dc.subject.meshMembrane Potentials - Drug Effects
 
dc.subject.meshMiddle Aged
 
dc.subject.meshMuscle, Smooth, Vascular - Cytology - Drug Effects - Physiology
 
dc.subject.meshMyocytes, Smooth Muscle - Drug Effects - Metabolism - Physiology
 
dc.subject.meshPeptides - Pharmacology
 
dc.subject.meshPhorbol Esters - Pharmacology
 
dc.subject.meshPotassium Channels, Calcium-Activated - Antagonists & Inhibitors - Metabolism - Physiology
 
dc.subject.meshProtein Kinase C-Delta - Metabolism
 
dc.subject.meshPyridines - Pharmacology
 
dc.subject.meshSimvastatin - Chemistry - Pharmacology
 
dc.subject.meshSwine
 
dc.titleModulation by simvastatin of iberiotoxin-sensitive, Ca 2+- activated K + channels of porcine coronary artery smooth muscle cells
 
dc.typeArticle
 
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<description.abstract>Background and Purpose: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors) have been demonstrated to reduce cardiovascular mortality. It is unclear how the expression level of HMG CoA reductase in cardiovascular tissues compares with that in cells derived from the liver. We hypothesized that this enzyme exists in different cardiovascular tissues, and simvastatin modulates the vascular iberiotoxin-sensitive Ca 2+- activated K + (BK Ca) channels. Experimental Approaches: Expression of HMG CoA reductase in different cardiovascular preparations was measured. Effects of simvastatin on BK Ca channel gatings of porcine coronary artery smooth muscle cells were evaluated. Key Results: Western immunoblots revealed the biochemical existence of HMG CoA reductase in human cardiovascular tissues and porcine coronary artery. In porcine coronary artery smooth muscle cells, extracellular simvastatin (1, 3 and 10 &#956;M) (hydrophobic), but not simvastatin Na + (hydrophilic), inhibited the BK Ca channels with a minimal recovery upon washout. Isopimaric acid (10 &#956;M)-mediated enhancement of the BK Ca amplitude was reversed by external simvastatin. Simvastatin Na + (10 &#956;M, applied internally), markedly attenuated isopimaric acid (10 &#956;M)-induced enhancement of the BK Ca amplitude. Reduced glutathione (5 mM; in the pipette solution) abolished simvastatin -elicited inhibition. Mevalonolactone (500 &#956;M) and geranylgeranyl pyrophosphate (20 &#956;M) only prevented simvastatin (1 and 3 &#956;M)-induced responses. simvastatin (10 &#956;M) caused a rottlerin (1 &#956;M)-sensitive (cycloheximide (10 &#956;M)-insensitive) increase of PKC-&#948; protein expression. Conclusions and Implications: Our results demonstrated the biochemical presence of HMG CoA reductase in different cardiovascular tissues, and that simvastatin inhibited the BK Ca channels of the arterial smooth muscle cells through multiple intracellular pathways. &#169; 2007 Nature Publishing Group All rights reserved.</description.abstract>
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Author Affiliations
  1. The University of Hong Kong
  2. Union Hospital
  3. Prince of Wales Hospital Hong Kong
  4. University of Macau
  5. Hong Kong Polytechnic University
  6. Chinese University of Hong Kong