title: Reduced SIRT1 expression correlates with enhanced oxidative stress in compensated and decompensated heart failure.
abstract: Sirtuin-1 (SIRT1) is a longevity factor in mammals initiating the cell survival mechanisms, and preventing ischemic injury in heart. In the etiopathogenesis of heart failure (HF), impairment in cardiomyocyte survival is a notable factor. Oxidative stress comprises a critical impact on cardiomyocyte lifespan in HF. The aim of the present study was to investigate SIRT1 expression in patients with compensated (cHF) and decompensated HF (dHF), and its correlation with oxidative stress. SIRT1 expression in peripheral leukocytes was examined using quantitative RT-PCR in 163 HF patients and 84 controls. Serum total oxidant status (TOS) and total antioxidant status (TAS) were measured via colorimetric assays, and oxidative stress index (OSI) was calculated. Lipid parameters were also determined by routine laboratory methods. SIRT1 mRNA expression was significantly downregulated in HF with more robust decrease in dHF (p=0.002, control vs cHF; p<0.001, control vs dHF). Markedly increased oxidative stress defined as elevated TOS, OSI and low TAS levels were detected in HF patients comparing with the controls (TAS; p=0.010, control vs cHF, p=0.045 control vs dHF, TOS; p=0.004 control vs cHF; p<0.001 control vs dHF, OSI; p<0.001 for both comparisons, respectively). With SIRT1 expression levels, TAS, TOS, OSI, and high density lipoprotein levels in cHF and dHF were determined correlated. SIRT1 expression were significantly reduced in both HF subtypes, particularly in dHF. SIRT1 expression was correlated with the oxidant levels and antioxidant capacity. Data suggest that SIRT1 may have a significant contribution in regulation of oxidant/antioxidant balance in HF etiology and compensation status.
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Harran University, Sanliurfa 63300, Turkey. Electronic address: feridunakkafa@yandex.com.
authors.forename: Feridun
authors.initials: F
authors.lastname: Akkafa
authors.affiliation: Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Halil Altiparmak
authors.affiliation: Department of Cardiology, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Musluhittin Emre
authors.initials: ME
authors.lastname: Erkus
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Nurten
authors.initials: N
authors.lastname: Aksoy
authors.affiliation: Department of Cardiology, M. Akif Inan Training and Research Hospital, Sanliurfa, Turkey.
authors.forename: Caner
authors.initials: C
authors.lastname: Kaya
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozer
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Sezen
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Oztuzcu
authors.affiliation: Department of Molecular Biology, Faculty of Science, Harran University, Sanliurfa, Turkey.
authors.forename: Ismail
authors.initials: I
authors.lastname: Koyuncu
authors.affiliation: Institute of Health Sciences, Harran University, Sanliurfa, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Umurhan
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D015870:Gene Expression; D006333:Heart Failure / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics*; D012720:Severity of Illness Index; D056564:Sirtuin 1 / Q000097:blood / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012333:RNA, Messenger; D014280:Triglycerides; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: HDL; OSI; RT-qPCR; Sirtuin; TAS; TOS