Qiang Su

Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization

We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1xa0week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10xa0mg/kg) 30xa0min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (Pxa0<xa00.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (Pxa0<xa00.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (Pxa0<xa00.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (Pxa0<xa00.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.

Endothelial microparticles exert differential effects on functions of Th1 in patients with acute coronary syndrome

BACKGROUNDnEndothelial microparticles (EMPs) can be involved in inflammatory process, blood coagulation, and regulation of vascular function. However, it remains unclear whether EMPs participate in the pathogenesis of ACS. The purpose of this study is to investigate the impact of EMPs on Th1/Th2 development and functions in vitro.nnnMETHODSnEight-five patients were allocated into SAP group (n=27), UAP group (n=28), and AMI group (n=30). Twenty hospitalized patients with normal coronary angiography were recruited as controls. The frequency of EMPs, IFN-γ, and IL-4 levels were measured, and the correlation between EMPs and Th1/Th2 cytokine was analyzed. PBMCs isolated from patients with ACS were treated in vitro with EMPs. This was followed by flow cytometry for Th1/Th2 counts, real-time PCR and western blotting for T-bet and GATA mRNA and protein expression, and ELISA for IFN-γ, TNF-α, IL-4, and IL-10.nnnRESULTSnThis study proved that the frequency of EMPs was significantly increased in ACS patients. There was a significant positive correlation between EMPs and IFN-γ. EMPs could significantly upregulate the differentiation and function of Th1 through increasing the expression of T-bet mRNA and protein. Furthermore, this study also indicated that EMP treatment in vitro could promote the expression of TNF-α, which exerts adverse effects on the pathogenesis and progression of atherosclerosis.nnnCONCLUSIONSnEMPs may be involved in the immune and inflammatory processes that take part in artery atherosclerosis and that they do so by regulating Th1/Th2 differentiation and function. They may play an important role in the pathogenesis of coronary atherosclerosis and plaque instability.

MiR-486 regulates cardiomyocyte apoptosis by p53-mediated BCL-2 associated mitochondrial apoptotic pathway

BackgroundCardiomyocyte apoptosis is a common pathological manifestation that occurs in several heart diseases. This study aimed to explore the mechanism of microRNA-486 (miR-486) in cardiomyocyte apoptosis by interfering with the p53-activated BCL-2 associated mitochondrial pathway.MethodsmiR-486 mimics and inhibitors were transfected into the primary cardiomyocytes of suckling Sprague-Dawley rat pups, and H2O2 was used to induce apoptosis. Flow cytometry and TUNEL were both used to detect cardiomyocyte apoptosis, while the relative mRNA transcript and protein levels of miR-486, p53, Bbc3, BCL-2, and cleaved caspase-3 were detected using RT-PCR and western blot analysis, respectively.ResultsmiR-486 overexpression significantly decreased the expressions of p53, Bbc3 and cleaved caspase-3 (Pxa0<xa00.05), and BCL-2 expression was significantly increased (Pxa0<xa00.05), which in turn caused a significant decrease in the rate of cardiomyocyte apoptosis (Pxa0<xa00.05). In contrast, miR-486 silencing resulted in an elevated rate of cardiomyocyte apoptosis (Pxa0<xa00.05).ConclusionmiR-486 may regulate cardiomyocyte apoptosis via p53-mediated BCL-2 associated mitochondrial apoptotic pathway. Therefore, up-regulating miR-486 expression in cardiomyocytes can effectively reduce the activation of the BCL-2 associated mitochondrial apoptotic pathway, consequently protecting cardiomyocytes.

Upregulation of miR-155 in CD4+ T Cells Promoted Th1 Bias in Patients With Unstable Angina

An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4+ T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4+ T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4+ T cells revealed that miR‐155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR‐155 expression was positively correlated with the percentage of Th1 cells and interferon‐gamma (IFN‐γ) levels in patients with UA. In addition, overexpression of miR‐155 in human circulating CD4+ T cells promoted Th1 differentiation. Further studies identified IFN‐γ receptor alpha chain (IFN‐γ Rα) mRNA as a direct and functional target of miR‐155. A luciferase reporter assay verified that miR‐155 directly targeted IFN‐γ Rα mRNA. Small‐interfering RNA‐mediated knockdown of IFN‐γ Rα mRNA showed effects similar to those of ectopic miR‐155 expression. Thus, our study indicated that upregulation of miR‐155 in circulating CD4+ T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN‐γ Rα, which may subsequently enhance plaque instability. J. Cell. Physiol. 230: 2498–2509, 2015.

Safety and Effectiveness of Nitroprusside in Preventing No-Reflow During Percutaneous Coronary Intervention: A Systematic Review

The objective of this study was to evaluate the clinical efficacy and safety of nitroprusside injection for preventing the slow-flow/no-reflow phenomenon after percutaneous coronary intervention (PCI). We searched the Cochrane Central Register of Controlled Trials (Issue 2, 2011), PubMed, EMbase, and Google Scholar for data. Two reviewers independently evaluated the quality of the included studies and extracted the data. A meta-analysis was performed using RevMan 5.0 software. Four randomized controlled trials (RCTs) involving 319 patients were included. The results of the meta-analyses showed that intracoronary nitroprusside is beneficial in preventing no-reflow/slow-flow, in reducing corrected TIMI frame count, and in improving left ventricular ejection fraction. It also likely reduces adverse reactions in patients after PCI and rehospitalization due to cardiovascular events. However, we must caution that in this review, there is a moderate possibility of bias with regard to patient selection, performance, and publication because of the small number of included studies. A larger sample size and high-quality RCTs are needed for a more reassuring analysis.

Comparative Efficacy and Safety of Drug-Eluting Stent and Conventional Therapies in Coronary Heart Disease Patients with In-Stent Restenosis: A Meta-Analysis

We performed a meta-analysis to compare therapeutic outcome/safety of drug-eluting stent (DES) and conventional in-stent restenosis (ISR) treatments. We browsed through large volume of clinical data by searching MEDLINE, EMBASE, Cochrane central register of controlled trials, and EBSCO databases. In this study, 11 randomized controlled trials, 17 non-randomized controlled trials, 6,330 patients, and 6,662 lesions were included. Clinical and coronary angiography follow-up for 6–16xa0months was included. The major outcomes were target lesion revascularization (TLR) and major adverse cardiac events (MACE). We found that DES showed advantage in TLR (ORxa0=xa00.46; 95xa0% CI: 0.34, 0.62; Pxa0<xa00.00001), MACE (ORxa0=xa00.51; 95xa0% CI: 0.34, 0.77; Pxa0=xa00.001), Late Lumen Loss (IVxa0=xa0−0.30; 95xa0% CI: −0.44, −0.15; Pxa0<xa00.0001), stenosis of lumen diameter (ORxa0=xa0−17.45; 95xa0% CI: −23.69, −11.21; Pxa0<xa00.00001), and restenosis (ORxa0=xa00.26; 95xa0% CI: 0.17, 0.40; Pxa0<xa00.00001) over conventional ISR treatment. Regarding cardiac death (ORxa0=xa00.80; 95xa0% CI: 0.55, 1.17; Pxa0=xa00.25), myocardial infarction (ORxa0=xa01.00;95xa0%CI: 0.66, 1.51; Pxa0=xa01.00) and late thrombosis (ORxa0=xa00.70; 95xa0% CI: 0.42, 1.17; Pxa0=xa00.18), there was no significant difference between different treatments. We, therefore, concluded that in treating percutaneous coronary intervention–ISR, DES was more effective in reducing incidence of TLR, MACE, and restenosis, and decreasing severity of late lumen loss/stenosis of lumen diameter compared with bare metal stent, percutaneous transluminal coronary angioplasty, intracoronary brachytherapy, and cutting balloon treatments. There was no significant difference between DES and conventional therapy for ISR. As suggested by current statistical analysis, DES after ISR did not involve a higher incidence of cardiac death, myocardial infarction, and thrombosis.

The clinical effect of nicorandil on perioperative myocardial protection in patients undergoing elective PCI: A Systematic Review and Meta-Analysis

Many scholars have studied the effect of nicorandil on perioperative myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI), but results are inconsistent. Therefore, we performed this meta-analysis. Finally, 16 articles, including 1616 patients, were included into this meta-analysis. Meta-analysis results showed that: (1) Nicorandil can reduce the level of CK-MB after PCI, including at 6u2009hours, 12u2009hours, 18u2009hours and 24u2009hours. (2) Nicorandil can reduce the level of TnT after PCI, including at 6u2009hours, 12u2009hours, 18u2009hours and 24u2009hours. (3) Nicorandil can reduce the incidence of adverse reactions after PCI. (4) Nicorandil cannot reduce the level of MVP after PCI, including at 12u2009hours and 24u2009hours. (5) Subgroup analysis showed that nicorandil can reduce CK-MB and TnT level at 24u2009hours after PCI for Chinese’s population (Pu2009<u20090.05), but can not reduce CK-MB and TnT level at 24u2009hours after PCI for non Chinese’s population (Pu2009>u20090.05). Our meta-analysis indicate that nicorandil can reduce myocardial injury and reduce the incidence of adverse reaction caused by PCI for Chinese’s population, but is not obvious for non Chinese’s population. However, this conclusion still needs to be confirmed in the future.

Pinocembrin protects endothelial cells from oxidized LDL-induced injury

HighlightsPinocembrin inhibits the induction of VCAM‐1, ICAM‐1, and E‐selectin by ox‐LDL.Pinocembrin ameliorates ox‐LDL‐induced attachment of monocytes to endothelial cells.Pinocembrin suppresses ox‐LDL induced production of pro‐inflammatory cytokines.Pinocembrin attenuates ox‐LDL induced production of ROS in HAECs.Pinocembrin inhibits ox‐LDL‐induced activation of p38 and IKK&agr;/I&kgr;B&agr;/NF‐&kgr;B signaling. Abstract Oxidized low‐density lipoprotein (ox‐LDL) is a major risk factor for atherosclerosis and often causes injury to vascular endothelial cells. We found that pinocembrin, a natural antioxidant found in honey and certain herbs, protects human aortic endothelial cells (HAECs) from ox‐LDL‐induced injury. Pinocembrin suppresses the expression of pro‐inflammatory vascular adhesion molecules (VCAM‐1, ICAM‐1 and E‐selectin) and cytokines (TNF‐&agr;, IL‐1&bgr;, and IL‐8), as well as ROS production induced by ox‐LDL. Pinocembrin potently inhibits the attachment of monocytes to HAEC cells. Mechanistically, pinocembrin suppresses activation of the MAPK kinase p38 and NF‐&kgr;B pathways in the context of ox‐LDL. Our data indicate that pinocembrin is a promising versatile natural compound that can protect endothelial cells from injury.

The protective effect of nicorandil on cardiomyocyte apoptosis after coronary microembolization by activating Nrf2/HO-1 signaling pathway in rats

BACKGROUNDnMyocardial apoptosis is considered to be the chief cause of progressive cardiac dysfunction induced by coronary microembolization (CME), and the Nrf2/HO-1 signaling pathway is involved in CME-induced myocardial apoptosis. Nicorandil (NIC) has multiple beneficial cardiovascular effects on myocardial injury. Therefore, this study was undertaken to analyze the role of NIC pretreatment in the inhibiting myocardial apoptosis after CME in rats.nnnMETHODSnForty rats were divided into Sham group, CME group, CME plus NIC (NIC) group, and CME plus AAV9-Nrf2 (AAV9-Nrf2) group (nu202f=u202f10 per group). CME-induced myocardial apoptosis model was established through injecting plastic microspheres (42u202fμM) into the left ventricle except the Sham group. NIC group received nicorandil 3u202fmg/(kg.d) for 7 days before the operation. Cardiac function was assessed by echocardiography. The mRNA expression level of Nrf2 was detected by RT-PCR. The protein expression levels of Nrf2, HO-1, Bcl-2, Bax and cleaved caspase-3 were detected by Western blot. The size of the microinfarction area was measured by HBFP staining; myocardial apoptosis was analyzed by TUNEL staining.nnnRESULTSnCompared with the sham group, the cardiac function and the expression level of Nrf2, HO-1 and Bcl-2were decreased, while myocardial apoptosis and the expression of Bax and cleaved caspase-3 were increased in the CME group. Compared with the CME group, cardiac function was significantly improved, the expression levels of Nrf2, HO-1, and Bcl-2 were increased, the expression of Bax and cleaved caspase-3 were decreased, and the myocardial apoptosis was attenuated in the NIC group and AAV9-Nrf2 group.nnnCONCLUSIONnNIC pretreatment effectively inhibit CME-induced myocardial apoptosis and improve cardiac function. The protective effects are mediated through the activation of the Nrf2/HO-1 signaling in cardiomyocytes.

The protective effect of activating Nrf2 / HO-1 signaling pathway on cardiomyocyte apoptosis after coronary microembolization in rats

BackgroundMyocardial apoptosis is closely related to myocardial injury caused by coronary microembolization (CME).Nuclear factor erythroid 2-like (Nrf2) has been taken into account as an inhibitor of apoptosis in various tissues. Thus, this research aims to investigate which part Nrf2/HO-1 signaling pathway plays in myocardial apoptosis process following the effect of CME on rats.MethodsSeparate 40 rats then form them into a group of shame, a group of CME, a group of CME plus AAV-Nrf2(AAV-Nrf2 (CME) group) and a group of CME plus AAV-control (AAV-control (CME) group) stochastically and averagely. Rat CME was established by injecting into the left ventricular chamber, with or without pretreatment of adeno-associated virus Nrf2 (AAV-Nrf2). Echocardiological measurements, using Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) to stain, conducting Quantitative PCR in real time (RT-PCR) as well as Western blotting to evaluate the impacts of them functionally, morphologically and molecularly in CME.ResultsNrf2 decreased in cardiomyocytes after CME. Upregulation of Nrf2 inside an organism through AAV connect to improving the function of heart as well as attenuating myocardial apoptosis, following the restrain of proapoptotic mRNAs and proteins like caspase-3, caspase-9 and bax expressing as well as the increase of antiapoptotic mRNA and proteins like HO-1 and bcl-2 expressing.ConclusionActivation of Nrf2/HO-1 pathway can improve CME-induced cardiac dysfunction effectively and also reduce the myocardial apoptosis.