The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA
Plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom - dokazi dobijeni analizom veličine i raspodele subfrakcija lipoproteina velike gustine i plazmatske mRNA
2015
Autori
Mirjanić-Azarić, BosaJelić-Ivanović, Zorana
Zeljković, Aleksandra
Vekić, Jelena
Juergens, Guenther
Milivojac, Tatjana
Avram, Sanja
Ćorić, Jozo
Marc, Janja
Černe, Darko
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Background: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B). Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses. Results: In group A, after therapy, HDL-C concentrat...ion was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p = 0.023) and significantly increased after therapy. Conclusions: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy.
Uvod: Lipoproteini velike gustine (HDL) imaju ateroprotektivne biološke osobine: antioksidativne, antiapoptotičke, antiinflamatorne kao i kapacitet da izvlače holesterol iz ćelija. Analiza plazmatske mRNA može da se koristi za ispitivanje plejotropnih efekata statina in vivo kao novo analitičko sredstvo za neinvazivnu procenu ekspresije gena u zidu krvnog suda. Cilj ove studije je bio da se procene plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom sa visokorizičnim vrednostima (grupa A) u odnosu na pacijente sa graničnim i poželjnim vrednostima HDL holesterola (HDLC) (grupa B). Metode: Četrdeset tri pacijenta sa stabilnom anginom su primala terapiju atorvastatinom (20 mg/dan) 10 nedelja. Mi smo ispitivali tri gena značajna za plejotropno delovanje statina: intracelularni adhezioni molekul-1, hemokin (C-C motiv) ligand 2 i katepsin S i procenjivali smo efekte atorvastatina na veličinu i raspodelu HDL subfrakcija pomoću elektroforeze na poliakrilamidnom gradijent gelu.... Rezultati: U grupi A, posle terapije, HDL-C koncentracija se značajno povećala, ali ne i u grupi B. Atorvastatin je snizio plazmatski nivo hemokin (C-C motiv) liganda 2 i intracelularnog adhezionog molekula-1 mRNA u obe grupe, ali nije promenio plazmatski nivo gena za katepsin S. Samo u grupi A, ukupni bilirubin je pokazao negativnu korelaciju sa genom za katepsin S (r = -0,506; p = 0,023) pre započinjanja terapije i značajni porast nakon terapije atorvastatinom. Zaključak: HDL-C i bilirubin mogu biti obećavajući terapijski ciljevi u lečenju kardiovaskularnih bolesti. Analiza slobodne mRNA (eng. cell-free mRNA) u plazmi može postati korisno sredstvo za procenu plejotropnog delovanja statina.
Ključne reči:
high-density lipoprotein subclasses / cathepsin S / bilirubin / mRNA in plasma / atorvastatin / subfrakcije lipoproteina velike gustine / katepsin S / bilirubin / mRNA u plazmi / atorvastatinIzvor:
Journal of Medical Biochemistry, 2015, 34, 3, 314-322Izdavač:
- Društvo medicinskih biohemičara Srbije, Beograd i Versita
Finansiranje / projekti:
- Ad Futura - Scientific and Educational Foundation of the Republic of Slovenia, by the Slovenian Research Agency grant P4-0127 and project BI-RS/12-13-048
- Interaktivna uloga dislipidemije, oksidativnog stresa i inflamacije u aterosklerozi i drugim bolestima: genetički i biohemijski markeri (RS-MESTD-Basic Research (BR or ON)-175035)
DOI: 10.2478/jomb-2014-0058
ISSN: 1452-8258
PubMed: 28356842
WoS: 000358329200006
Scopus: 2-s2.0-84938368275
Institucija/grupa
PharmacyTY - JOUR AU - Mirjanić-Azarić, Bosa AU - Jelić-Ivanović, Zorana AU - Zeljković, Aleksandra AU - Vekić, Jelena AU - Juergens, Guenther AU - Milivojac, Tatjana AU - Avram, Sanja AU - Ćorić, Jozo AU - Marc, Janja AU - Černe, Darko PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2432 AB - Background: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B). Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses. Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p = 0.023) and significantly increased after therapy. Conclusions: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy. AB - Uvod: Lipoproteini velike gustine (HDL) imaju ateroprotektivne biološke osobine: antioksidativne, antiapoptotičke, antiinflamatorne kao i kapacitet da izvlače holesterol iz ćelija. Analiza plazmatske mRNA može da se koristi za ispitivanje plejotropnih efekata statina in vivo kao novo analitičko sredstvo za neinvazivnu procenu ekspresije gena u zidu krvnog suda. Cilj ove studije je bio da se procene plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom sa visokorizičnim vrednostima (grupa A) u odnosu na pacijente sa graničnim i poželjnim vrednostima HDL holesterola (HDLC) (grupa B). Metode: Četrdeset tri pacijenta sa stabilnom anginom su primala terapiju atorvastatinom (20 mg/dan) 10 nedelja. Mi smo ispitivali tri gena značajna za plejotropno delovanje statina: intracelularni adhezioni molekul-1, hemokin (C-C motiv) ligand 2 i katepsin S i procenjivali smo efekte atorvastatina na veličinu i raspodelu HDL subfrakcija pomoću elektroforeze na poliakrilamidnom gradijent gelu. Rezultati: U grupi A, posle terapije, HDL-C koncentracija se značajno povećala, ali ne i u grupi B. Atorvastatin je snizio plazmatski nivo hemokin (C-C motiv) liganda 2 i intracelularnog adhezionog molekula-1 mRNA u obe grupe, ali nije promenio plazmatski nivo gena za katepsin S. Samo u grupi A, ukupni bilirubin je pokazao negativnu korelaciju sa genom za katepsin S (r = -0,506; p = 0,023) pre započinjanja terapije i značajni porast nakon terapije atorvastatinom. Zaključak: HDL-C i bilirubin mogu biti obećavajući terapijski ciljevi u lečenju kardiovaskularnih bolesti. Analiza slobodne mRNA (eng. cell-free mRNA) u plazmi može postati korisno sredstvo za procenu plejotropnog delovanja statina. PB - Društvo medicinskih biohemičara Srbije, Beograd i Versita T2 - Journal of Medical Biochemistry T1 - The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA T1 - Plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom - dokazi dobijeni analizom veličine i raspodele subfrakcija lipoproteina velike gustine i plazmatske mRNA VL - 34 IS - 3 SP - 314 EP - 322 DO - 10.2478/jomb-2014-0058 ER -
@article{ author = "Mirjanić-Azarić, Bosa and Jelić-Ivanović, Zorana and Zeljković, Aleksandra and Vekić, Jelena and Juergens, Guenther and Milivojac, Tatjana and Avram, Sanja and Ćorić, Jozo and Marc, Janja and Černe, Darko", year = "2015", abstract = "Background: High-density lipoproteins (HDL) have atheroprotective biological properties: antioxidative, anti-apoptotic, anti-inflammatory, and they have the efflux capacity of cellular cholesterol. Plasma mRNA analysis can be used to investigate statin pleiotropy in vivo as a new analytical tool for non-invasive assessment of gene expression in vascular beds. The aim of this study was to assess the pleiotropic effects of atorvastatin in stable angina patients with highrisk values (group A) as compared with patients who had borderline and desirable HDL-cholesterol (HDL-C) values (group B). Methods: The atorvastatin therapy (20 mg/day) was given to forty-three patients with stable angina for 10 weeks. We investigated three statin pleiotropy-targeted genes: intercellular adhesion molecule-1, chemokine (C-C motif) ligand 2 and cathepsin S and assessed by gel electrophoresis gradient the effects of atorvastatin on HDL size and subclasses. Results: In group A, after therapy, HDL-C concentration was significantly increased but not in group B. Atorvastatin lowered plasma chemokine (C-C motif) ligand 2 and intercellular adhesion molecule-1 mRNA levels in both groups, but did not change the plasma cathepsin S mRNA levels. In group A only, baseline total bilirubin showed negative cor relations with the genes of cathepsin S (r=-0.506; p = 0.023) and significantly increased after therapy. Conclusions: HDL-C and bilirubin can be promising therapeutic targets in the treatment of cardiovascular diseases. Analysis of cell-free mRNA in plasma might become a useful tool for estimating statin pleiotropy., Uvod: Lipoproteini velike gustine (HDL) imaju ateroprotektivne biološke osobine: antioksidativne, antiapoptotičke, antiinflamatorne kao i kapacitet da izvlače holesterol iz ćelija. Analiza plazmatske mRNA može da se koristi za ispitivanje plejotropnih efekata statina in vivo kao novo analitičko sredstvo za neinvazivnu procenu ekspresije gena u zidu krvnog suda. Cilj ove studije je bio da se procene plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom sa visokorizičnim vrednostima (grupa A) u odnosu na pacijente sa graničnim i poželjnim vrednostima HDL holesterola (HDLC) (grupa B). Metode: Četrdeset tri pacijenta sa stabilnom anginom su primala terapiju atorvastatinom (20 mg/dan) 10 nedelja. Mi smo ispitivali tri gena značajna za plejotropno delovanje statina: intracelularni adhezioni molekul-1, hemokin (C-C motiv) ligand 2 i katepsin S i procenjivali smo efekte atorvastatina na veličinu i raspodelu HDL subfrakcija pomoću elektroforeze na poliakrilamidnom gradijent gelu. Rezultati: U grupi A, posle terapije, HDL-C koncentracija se značajno povećala, ali ne i u grupi B. Atorvastatin je snizio plazmatski nivo hemokin (C-C motiv) liganda 2 i intracelularnog adhezionog molekula-1 mRNA u obe grupe, ali nije promenio plazmatski nivo gena za katepsin S. Samo u grupi A, ukupni bilirubin je pokazao negativnu korelaciju sa genom za katepsin S (r = -0,506; p = 0,023) pre započinjanja terapije i značajni porast nakon terapije atorvastatinom. Zaključak: HDL-C i bilirubin mogu biti obećavajući terapijski ciljevi u lečenju kardiovaskularnih bolesti. Analiza slobodne mRNA (eng. cell-free mRNA) u plazmi može postati korisno sredstvo za procenu plejotropnog delovanja statina.", publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita", journal = "Journal of Medical Biochemistry", title = "The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA, Plejotropni efekti atorvastatina kod pacijenata sa stabilnom anginom - dokazi dobijeni analizom veličine i raspodele subfrakcija lipoproteina velike gustine i plazmatske mRNA", volume = "34", number = "3", pages = "314-322", doi = "10.2478/jomb-2014-0058" }
Mirjanić-Azarić, B., Jelić-Ivanović, Z., Zeljković, A., Vekić, J., Juergens, G., Milivojac, T., Avram, S., Ćorić, J., Marc, J.,& Černe, D.. (2015). The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA. in Journal of Medical Biochemistry Društvo medicinskih biohemičara Srbije, Beograd i Versita., 34(3), 314-322. https://doi.org/10.2478/jomb-2014-0058
Mirjanić-Azarić B, Jelić-Ivanović Z, Zeljković A, Vekić J, Juergens G, Milivojac T, Avram S, Ćorić J, Marc J, Černe D. The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA. in Journal of Medical Biochemistry. 2015;34(3):314-322. doi:10.2478/jomb-2014-0058 .
Mirjanić-Azarić, Bosa, Jelić-Ivanović, Zorana, Zeljković, Aleksandra, Vekić, Jelena, Juergens, Guenther, Milivojac, Tatjana, Avram, Sanja, Ćorić, Jozo, Marc, Janja, Černe, Darko, "The Pleiotropic Effects of Atorvastatin on Stable Angina Patients: Evidence by Analysis of High-Density Lipoprotein Size and Subclasses, and Plasma mRNA" in Journal of Medical Biochemistry, 34, no. 3 (2015):314-322, https://doi.org/10.2478/jomb-2014-0058 . .