Chromosomal damage and atherosclerosis. A protective effect from simvastatin
In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the ef...
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| creator | Pernice, Franco Floccari, Fulvio Caccamo, Chiara Belghity, Nadia Mantuano, Stefania Pacilè, Maria Elisa Romeo, Adolfo Nostro, Lorena Barillà, Antonio Crascì, Eleonora Frisina, Nicola Buemi, Michele |
| description | In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage.
Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration.
Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82
±
2.1 vs. 4.65
±
2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage.
Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients.
In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity.
Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque. |
| doi_str_mv | 10.1016/j.ejphar.2006.01.003 |
| format | Article |
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Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration.
Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82
±
2.1 vs. 4.65
±
2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage.
Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients.
In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity.
Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2006.01.003</identifier><identifier>PMID: 16483569</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Atherosclerosis ; Atherosclerosis (general aspects, experimental research) ; Atherosclerosis - blood ; Atherosclerosis - genetics ; Atherosclerosis - pathology ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Carotid Arteries - diagnostic imaging ; Carotid Arteries - pathology ; Cells, Cultured ; Chromosome Aberrations - drug effects ; Dialysis ; Dose-Response Relationship, Drug ; Female ; Genomic damage ; Hemodiafiltration ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Kidney Failure, Chronic - blood ; Kidney Failure, Chronic - genetics ; Kidney Failure, Chronic - therapy ; Lymphocytes - drug effects ; Male ; Medical sciences ; Middle Aged ; Mitotic Index ; Pharmacology. Drug treatments ; Simvastatin ; Simvastatin - pharmacology ; Sister chromatid exchange ; Sister Chromatid Exchange - drug effects ; Ultrasonography</subject><ispartof>European journal of pharmacology, 2006-02, Vol.532 (3), p.223-229</ispartof><rights>2006 Elsevier B.V.</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-41a165e0b4476752c9f91b2b37c2f6d0e58865788cd019dbb27116223a3bba9a3</citedby><cites>FETCH-LOGICAL-c422t-41a165e0b4476752c9f91b2b37c2f6d0e58865788cd019dbb27116223a3bba9a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2006.01.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17541304$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16483569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pernice, Franco</creatorcontrib><creatorcontrib>Floccari, Fulvio</creatorcontrib><creatorcontrib>Caccamo, Chiara</creatorcontrib><creatorcontrib>Belghity, Nadia</creatorcontrib><creatorcontrib>Mantuano, Stefania</creatorcontrib><creatorcontrib>Pacilè, Maria Elisa</creatorcontrib><creatorcontrib>Romeo, Adolfo</creatorcontrib><creatorcontrib>Nostro, Lorena</creatorcontrib><creatorcontrib>Barillà, Antonio</creatorcontrib><creatorcontrib>Crascì, Eleonora</creatorcontrib><creatorcontrib>Frisina, Nicola</creatorcontrib><creatorcontrib>Buemi, Michele</creatorcontrib><title>Chromosomal damage and atherosclerosis. A protective effect from simvastatin</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage.
Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration.
Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82
±
2.1 vs. 4.65
±
2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage.
Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients.
In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity.
Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.</description><subject>Atherosclerosis</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Atherosclerosis - blood</subject><subject>Atherosclerosis - genetics</subject><subject>Atherosclerosis - pathology</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Cardiology. Vascular system</subject><subject>Carotid Arteries - diagnostic imaging</subject><subject>Carotid Arteries - pathology</subject><subject>Cells, Cultured</subject><subject>Chromosome Aberrations - drug effects</subject><subject>Dialysis</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Genomic damage</subject><subject>Hemodiafiltration</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Kidney Failure, Chronic - blood</subject><subject>Kidney Failure, Chronic - genetics</subject><subject>Kidney Failure, Chronic - therapy</subject><subject>Lymphocytes - drug effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mitotic Index</subject><subject>Pharmacology. Drug treatments</subject><subject>Simvastatin</subject><subject>Simvastatin - pharmacology</subject><subject>Sister chromatid exchange</subject><subject>Sister Chromatid Exchange - drug effects</subject><subject>Ultrasonography</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuv0zAQRi0E4pYL_wChbIBVwozj2PEG6ariJVViA2tr4kyoqzyKnVbi3-Oqle7ubjxenG8eR4i3CBUC6k-Hig_HPcVKAugKsAKon4kNtsaWYFA-FxsAVKW01t6JVykdAKCxsnkp7lCrtm603Yjddh-XaUnLRGPR00R_uKC5L2jdc1ySHy9vSFXxUBzjsrJfw5kLHob8K4YcLVKYzpRWWsP8WrwYaEz85lbvxe-vX35tv5e7n99-bB92pVdSrqVCQt0wdEoZbRrp7WCxk11tvBx0D9y0rW5M2_oe0PZdJw2ilrKmuuvIUn0vPl775pX-njitbgrJ8zjSzMspOaM0NCA1ZvLDk6Q22uZZOoPqCvp8b4o8uGMME8V_DsFdfLuDu_p2F98O0GXfOfbu1v_UTdw_hm6CM_D-BlDyNA6RZh_SI2cahTWozH2-cpy9nQNHl3zg2XMfYlbt-iU8vcl_3UufWw</recordid><startdate>20060227</startdate><enddate>20060227</enddate><creator>Pernice, Franco</creator><creator>Floccari, Fulvio</creator><creator>Caccamo, Chiara</creator><creator>Belghity, Nadia</creator><creator>Mantuano, Stefania</creator><creator>Pacilè, Maria Elisa</creator><creator>Romeo, Adolfo</creator><creator>Nostro, Lorena</creator><creator>Barillà, Antonio</creator><creator>Crascì, Eleonora</creator><creator>Frisina, Nicola</creator><creator>Buemi, Michele</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20060227</creationdate><title>Chromosomal damage and atherosclerosis. A protective effect from simvastatin</title><author>Pernice, Franco ; Floccari, Fulvio ; Caccamo, Chiara ; Belghity, Nadia ; Mantuano, Stefania ; Pacilè, Maria Elisa ; Romeo, Adolfo ; Nostro, Lorena ; Barillà, Antonio ; Crascì, Eleonora ; Frisina, Nicola ; Buemi, Michele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-41a165e0b4476752c9f91b2b37c2f6d0e58865788cd019dbb27116223a3bba9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Atherosclerosis</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Atherosclerosis - blood</topic><topic>Atherosclerosis - genetics</topic><topic>Atherosclerosis - pathology</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Cardiology. Vascular system</topic><topic>Carotid Arteries - diagnostic imaging</topic><topic>Carotid Arteries - pathology</topic><topic>Cells, Cultured</topic><topic>Chromosome Aberrations - drug effects</topic><topic>Dialysis</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Genomic damage</topic><topic>Hemodiafiltration</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Kidney Failure, Chronic - blood</topic><topic>Kidney Failure, Chronic - genetics</topic><topic>Kidney Failure, Chronic - therapy</topic><topic>Lymphocytes - drug effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mitotic Index</topic><topic>Pharmacology. Drug treatments</topic><topic>Simvastatin</topic><topic>Simvastatin - pharmacology</topic><topic>Sister chromatid exchange</topic><topic>Sister Chromatid Exchange - drug effects</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pernice, Franco</creatorcontrib><creatorcontrib>Floccari, Fulvio</creatorcontrib><creatorcontrib>Caccamo, Chiara</creatorcontrib><creatorcontrib>Belghity, Nadia</creatorcontrib><creatorcontrib>Mantuano, Stefania</creatorcontrib><creatorcontrib>Pacilè, Maria Elisa</creatorcontrib><creatorcontrib>Romeo, Adolfo</creatorcontrib><creatorcontrib>Nostro, Lorena</creatorcontrib><creatorcontrib>Barillà, Antonio</creatorcontrib><creatorcontrib>Crascì, Eleonora</creatorcontrib><creatorcontrib>Frisina, Nicola</creatorcontrib><creatorcontrib>Buemi, Michele</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pernice, Franco</au><au>Floccari, Fulvio</au><au>Caccamo, Chiara</au><au>Belghity, Nadia</au><au>Mantuano, Stefania</au><au>Pacilè, Maria Elisa</au><au>Romeo, Adolfo</au><au>Nostro, Lorena</au><au>Barillà, Antonio</au><au>Crascì, Eleonora</au><au>Frisina, Nicola</au><au>Buemi, Michele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chromosomal damage and atherosclerosis. A protective effect from simvastatin</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2006-02-27</date><risdate>2006</risdate><volume>532</volume><issue>3</issue><spage>223</spage><epage>229</epage><pages>223-229</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage.
Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration.
Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82
±
2.1 vs. 4.65
±
2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage.
Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients.
In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity.
Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>16483569</pmid><doi>10.1016/j.ejphar.2006.01.003</doi><tpages>7</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 2006-02, Vol.532 (3), p.223-229 |
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| subjects | Atherosclerosis Atherosclerosis (general aspects, experimental research) Atherosclerosis - blood Atherosclerosis - genetics Atherosclerosis - pathology Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Carotid Arteries - diagnostic imaging Carotid Arteries - pathology Cells, Cultured Chromosome Aberrations - drug effects Dialysis Dose-Response Relationship, Drug Female Genomic damage Hemodiafiltration Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Kidney Failure, Chronic - blood Kidney Failure, Chronic - genetics Kidney Failure, Chronic - therapy Lymphocytes - drug effects Male Medical sciences Middle Aged Mitotic Index Pharmacology. Drug treatments Simvastatin Simvastatin - pharmacology Sister chromatid exchange Sister Chromatid Exchange - drug effects Ultrasonography |
| title | Chromosomal damage and atherosclerosis. A protective effect from simvastatin |
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