[Expression of SIRT1 in right auricle tissues and the relationship with oxidative stress in patients with atrial fibrillation].

AIM: To observe the expression of mammalian sirtuin 1 (SIRT1) in right auricle tissues in patients presenting with atrial fibrillation (AF) and make clear the relationship between SIRT1 expression and oxidative stress. METHODS: A total of 38 patients with rheumatic heart disease were divided into 2 groups: AF group (AF lasted more than 6 months, n=25) and SR (sinus rhythm) group (n=13). The expression of SIRT1 in right auricle tissues harvested during heart operations was detected by immunohistochemistry. Oxidative stress was estimated by the amounts of malondialdehyde (MDA) and metallothionein (MT) and the activity of superoxide dismutase (SOD) which were detected using thiobarbituric acid reaction (TBA), enzyme-linked immunosorbent assay (ELISA) and xanthine oxidase assay, respectively. RESULTS: Compared with the SR group, the expression of SIRT1 protein in the atrium significantly increased in AF group [P<0.05, (45.8±4.03)% vs (19.7±2.54)%]. In AF group, MDA was (7.24±1.05) nmol/mg, SOD (1034.25±84.32) U/mg and MT (7.21±1.46) µg/g, all being significantly higher than those in SR group[P<0.05, MDA: (3.01±0.47) nmol/mg; SOD: (723.63±65.23) U/mg; MT: (4.31±1.23) µg/g]. Spearman correlation indicated that the expression of SIRT1 had a significantly negative correlation with the amounts of MDA and MT and the activity of SOD (P<0.05, r=-0.447, -0.521, -0.394, respectively). CONCLUSION: The expression of SIRT1 increased in patients with AF. SIRT1 maybe effects the AF by means of inhibiting the process of oxidative stress.

Antagonist of microRNA-21 improves balloon injury-induced rat iliac artery remodeling by regulating proliferation and apoptosis of adventitial fibroblasts and myofibroblasts.

Molecular pathways involved in adventitial fibroblasts (AFs) and myofibroblasts (MFs) proliferation and apoptosis contribute to vascular remodeling. MicroRNA-21 (miR-21) plays an important role in regulating cellular proliferation and apoptosis of many cell types; however, the effect of miR-21 on AFs and MFs is still unknown. In this study, we found that miR-21 was expressed in AFs and overexpressed in MFs. Inhibition of miR-21 decreased proliferation and increased apoptosis of AFs and MFs, and overexpression of miR-21 with pre-miR-21 had the reverse effect. Programmed cell death 4 (PDCD4), related to cell proliferation and apoptosis, was validated as a direct target of miR-21 by dual-luciferase reporter assay and gain and loss of function of miR-21 in AFs and MFs. PDCD4 knockdown with siRNA partly rescued the reduced proliferation with miR-21 inhibition and alleviated the increased apoptosis induced by miR-21 inhibition in AFs and MFs. Moreover, increasing PDCD4 expression by miR-21 inhibition significantly decreased JNK/c-Jun activity. In contrast, decreasing PDCD4 expression by pre-miR-21 treatment increased JNK/c-Jun activity, while the effect of miR-21 inhibition on JNK/c-Jun activity could be rescued by PDCD4 siRNA. Moreover, miR-21 inhibition could regulate proliferation and apoptosis of vascular AFs and MFs in vivo. Furthermore, miR-21 inhibition reversed vascular remodeling induced by balloon injury. In summary, our findings demonstrate that miR-21 may have a critical role in regulating proliferation and apoptosis of AFs and MFs, and PDCD4 is a functional target gene involved in the miR-21-mediated cellular effects in vascular remodeling by a miR-21/PDCD4/JNK/c-Jun pathway.

Rosiglitazone attenuates myocardial remodeling in spontaneously hypertensive rats.

Rosiglitazone, an important peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, improves left ventricular (LV) hypertrophy in diet-induced hypercholesterolemic rats. However, the effects and underlying mechanisms of rosiglitazone on myocardial remodeling in spontaneous hypertension rats (SHRs) are unclear. Twenty male 8-week-old SHRs were randomly divided into two groups: one treated with oral saline (n=10) and the other treated with rosiglitazone (5 mgkg(-1)day(-1), n=10). Ten age-matched Wistar-Kyoto rats were selected as a normal control group. Echocardiography, immunohistochemistry, real-time reverse transcriptase-PCR and western blot analysis were performed to assess the effects of rosiglitazone. After 16 weeks of treatment, LV hypertrophy was significantly attenuated by rosiglitazone (LV weight/body weight, 2.35±0.11 vs. 2.56±0.14 mgg(-1)). According to the echocardiography results, thickening of the LV wall was reduced, and mid-wall fractional shortening was improved by rosiglitazone. Similarly, the excessive collagen deposition and upregulation of collagen I and collagen III seen in SHRs receiving saline were significantly attenuated in SHRs receiving rosiglitazone. In addition, rosiglitazone treatment increased the activity of matrix metalloproteinase-9 (MMP-9) and normalized the MMP-9/tissue inhibitor of metalloproteinase-1 ratio. Furthermore, activator protein-1 (AP-1) activation and nuclear factor-kappa B (NF-κB) expression were suppressed in the rosiglitazone-treated group. These results demonstrate that the PPAR-γ agonist rosiglitazone had beneficial effects on myocardial remodeling in SHRs by way of decreasing AP-1 activation and NF-κB expression, which may help in further inhibiting transcription of the downstream genes involved in the pathogenesis of myocardial remodeling induced by hypertension.

[The correlation of human serum Lp-PLA2 and hs-CRP and stability of coronary atherosclerotic plaques].

OBJECTIVE: To explore the relationship of serum lipoprotein-associated phospholipase A2 and high sensitive C-reactive protein in vulnerable coronary atherosclerotic plaques. METHODS: Patients undergoing coronary angiography (CAG) were examined for CAD with intravascular ultrasound (IVUS). According to the findings of CAG and IVUS, all the patients were divided into three groups: a control group without plaque, stable plaque group and vulnerable plaque group. The total serum Lp-PLA2 and hs-CRP were measured before angiography and they were valued with T test and Pearson's correlation analysis. RESULTS: (1) Lp-PLA2 level in stable plaque group and vulnerable plaque group was higher than that in control group (P < 0.05). (2) Lp-PLA2 level in the vulnerable plaque group was higher than that in stable plaque group (P < 0.05). (3) hs-CRP level in the vulnerable plaque group is higher than that in the stable plaque group and control group (P < 0.05) and there was significant difference between them. (4) To discriminate vulnerable plaque, the specificity of serum Lp-PLA2 was stronger than that of hs-CRP. CONCLUSIONS: Serum Lp-PLA2 level has higher sensitivity in predicting the vulnerability of the coronary atherosclerotic plaque than hs-CRP. In combination with hs-CRP, we can use Lp-PLA2 as a new biomarker to predict the presence of vulnerable plaque.