Peripheral Blood Monocyte Sirt1 Expression Is Reduced in Patients with Coronary Artery Disease

Abstract

BackgroundInflammation plays a key role in atherosclerosis. Sirt1 regulates transcription factors involved in inflammatory processes and blunts atherosclerosis in mice. However, its role in humans remains to be defined. This study was therefore designed to investigate the role of Sirt1 in the development of atherosclerosis.Methods and Results48 male subjects admitted for cardiac catheterization were subdivided into healthy subjects, patients with stable coronary artery disease (CAD), and with acute coronary syndromes (ACS). Monocytes were isolated and Sirt1 mRNA levels were determined. Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS (P<0.05), respectively. Interestingly, HDL levels correlated positively with Sirt1 expression. Thus, HDL from the three groups was isolated and incubated with THP-1 monocytes to determine the effects of HDL on Sirt1 protein in controlled experimental conditions. HDL from healthy subjects stimulated Sirt1 expression in THP-1 monocytes to a higher degree than HDL from CAD and ACS patients (P<0.05). Paraoxonase-1 (PON-1), a HDL-associated enzyme, showed a reduced activity in HDL isolated from CAD and ACS patients as compared to the controls (P<0.001).ConclusionsMonocytic Sirt1 expression is reduced in patients with stable CAD and ACS. Experiments on THP-1 monocytes suggest that this effect is HDL-dependent and is mediated by a reduced activity of HDL-associated enzyme PON1.

Association between the <i>SIRT1</i> mRNA Expression and Acute Coronary Syndrome

“…It has also been reported that the blood levels of SIRT1 proteins are increased in patients suffering from cardiovascular disease (CVD) compared to that noted in healthy subjects 23) . These observations conflict with the results of our studies of ACS and another study of coronary artery disease 7) . In addition, we compared the mRNA expression levels of the SIRT1 gene in the AMI and UA patients and found that the SIRT1 expression levels were lower in the AMI patients than in the UA patients.…”

“…Our case-control study using gene expression microarrays and real-time PCR replication demonstrated that the SIRT1 mRNA expression level is associated with ACS, with a decreased expression in the PBMCs of the ACS patients, while earlier studies of the SIRT1 gene expression reported a reduced expression of the SIRT1 gene in monocytes derived from ACS patients 7) . PBMCs and monocytes are both cells related to the pathogenesis of ACS.…”

“…Stein S. et al 6) demonstrated that the SIRT1 protein expression in the aorta is lower in ApoE / mice than in wild-type mice and that SIRT1 retards the progression of atherosclerosis by preventing macrophage foam cell formation. Breitenstein A. et al 7) also found that the SIRT1 expression in monocytes to be decreased in 16 ACS patients. SIRT1 exerts atheroprotective effects on the vascular biology by downregulating the expression of various pro-inflammatory cytokines, mediating vasodilatation via the actions of eNOS-derived nitric oxide (NO) and scavenging reactive oxygen species (ROS) 8) .…”

“…We reviewed previous studies in order to examine whether the functions of the above 23 genes were related to ACS and found that the expression of SIRT1 gene had the greatest association evidence 7,21,22) . Our findings showed that the expression of the SIRT1 gene was reduced considerably in the patients suffering from AMI, UA and ACS compared with that observed in the control group.…”

Novel Role of Silent Information Regulator 1 in Myocardial Ischemia

“…Research data indicated that monocytic SIRT1 expression is reduced in patients with stable coronary artery disease and acute coronary syndromes. 80 Moreover, SIRT1 plays an important role in the prevention of atherosclerosis. Zeng and colleagues 81 reported that SIRT1 may prevent the formation and progression of atherosclerosis by enhancing the liver X receptor-ATP-binding cassette, A1/ABCG1/C-C chemokine receptor type 7, and inhibiting the NF-κB pathways.…”