Clinical utility of intravascular ultrasonography-guided therapy in a small-vessel coronary lesion associated with Type 2 diabetes mellitus.

OBJECTIVE: It is unknown whether the intravascular ultrasound (IVUS) guidance for percutaneous coronary intervention (PCI) should be routinely used in small-vessel coronary lesions in patients affected by Type 2 diabetes mellitus (T2DM). This study aimed to assess the clinical significance of the IVUS-guided PCI treatment for small-vessel coronary lesions in T2DM. METHODS: This was a prospective interventional trial. A total of 228 patients affected by T2DM with stable angina and a positive stress test in the presence of coronary arteriography (CAG) involving small vessels [online measurement reference vessel diameter ≤3.0 mm by means of quantitative coronary angiography (QCA)] were recruited and divided into two groups: an IVUS-guided group (n=120) and a CAG-guided group (n=108). Follow-up PCIs were performed via CAG or IVUS criteria, respectively. Between-group comparisons were made for the number of stents implanted, length, diameter, and high-pressure balloons used post-dilatation. Major adverse cardiac events (MACEs) defined as cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR) were the primary endpoint. The value of late lumen loss and proportion of in-stent restenosis (ISR) were the secondary endpoint, all of which were also evaluated during the follow-up period. RESULTS: There was an increased lesion length observed using the IVUS measurement when compared with QCA measurements in the IVUS-guided group (p≤0.001). The number of implanted stents, diameter, length, percentage of high-pressure balloons used during post-dilatation, value of late lumen loss, and proportion of ISR decreased in the IVUS-guided group when compared with the CAG-guided group (p=0.002, p=0.001, p=0.003, p=0.004, p=0.007, p=0.001, respectively). After a 2-year follow-up, the Kaplan-Meier curves indicated that the incidence of MACEs was significantly lower in the IVUS-guided group (log-rank p=0.029), mainly because of the TLR reduction (log-rank p=0.037). CONCLUSION: The IVUS-guided PCI treatment improved the event-free survival in small-vessel coronary lesions in patients affected by T2DM.

PM2.5 exposure aggravates left heart failure induced pulmonary hypertension.

Aim: Particulate matter 2.5 (PM2.5) exposure is high risk to cardiovascular diseases. We investigated the influence of PM2.5 exposure on pulmonary arterial hypertension (PAH) murine model induced by left ventricular (LV) failure. Methods: Thirty 10 weeks old C57BL/6 mice were randomised to four groups: sham group, sham + PM2.5 group, TAC group, and TAC + PM2.5 group. Eight weeks post TAC surgery, right ventricular (RV) and lung remodelling (Sirius Red staining and WGA Staining), heart and lung function (EF and RVSBP), and fibrotic genes (TGF-ti mRNA expression and collagen III protein level in lung tissue were measured. Results: Exposure to PM2.5 augments TAC induced PAH as evidenced by decreased EF value and increased RVSBP, RV cardiomyocytes size, RV and lung fibrosis, and upregulated expression of collagen III and TGF-a in comparison to TAC group in lung tissues. Even the LV EF value was deceased from 79.3 ± 3.4% to 63.4 ± 2.1% when sham group exposed to PM2.5, PM2.5 exposure had no effect on RVSBP, RV cardiomyocytes' size, RV weight/tibia length, RV and lung fibrosis, and expression of collagen III and TGF-a in sham surgery mice. Conclusions: Exposure to PM2.5 aggravates deterioration of LV failure induced PAH.

Percutaneous left ventricular assist device vs. intra-aortic balloon pump in patients with severe left ventricular dysfunction undergoing cardiovascular intervention: A meta-analysis.

OBJECTIVE: Although controversial, the intra-aortic balloon pump (IABP) and percutaneous left ventricular assist device (PLVAD) are widely used for initial hemodynamic stabilization. We performed a meta-analysis to compare the clinical outcomes of these two devices in patients with severe left ventricular (LV) dysfunction undergoing percutaneous coronary intervention (PCI) or ventricular tachycardia (VT) ablation. METHODS: MEDLINE, EMBASE, the Cochrane Registry of Controlled Trials, and reference lists of relevant articles were searched. We included randomized controlled trials (RCTs) and prospective observational studies. Meta-analysis was conducted using a random effects model. RESULTS: The quantitative analysis included 4 RCTs and 2 observational studies. A total of 348 patients received PLVAD and 340 received IABP. Meta-analysis revealed that early mortality rates (in-hospital or 30-day) did not differ between the PLVAD and IABP groups (relative risk (RR) = 1.03, 95% confidence interval (CI) = 0.70-1.51, P = 0.89). Significant differences were observed between the two groups in the composite, in-hospital, non-major adverse cardiac and cerebrovascular events (MACCE) rate (RR = 1.30, 95% CI = 1.01-1.68, P = 0.04). CONCLUSIONS: Compared with IABP, PLVAD with active circulatory support did not improve early survival in those with severe left ventricular dysfunction undergoing either PCI or VT ablation, but increased the in-hospital non-MACCE rate.

Apelin-13 attenuates cisplatin-induced cardiotoxicity through inhibition of ROS-mediated DNA damage and regulation of MAPKs and AKT pathways.

Platinum-based chemotherapy represents one of the most effective ways in combating human cancers. However, the cardiotoxicity subsequent severely limited its clinical application. Increased evidences indicate that oxidative stress plays a crucial role in the pathological process of platinum-induced cardiotoxicity. It is reported that apelin-13 a bioactive peptide has the scavenging capacity of free radical, and it has the potential to regulate the cardiovascular system. Hence, the potential of apelin-13 to antagonize cisplatin-induced cardiotoxicity was evaluated in H9c2 rat myocardial cells in vitro and in C57 mice in vivo. The results showed that cisplatin indeed caused DNA damage in H9c2 cells by promoting the accumulation of intracellular reactive oxygen species (ROS) and superoxide anion, which led to cell apoptosis and resulted in overt cardiotoxicity. However, apelin-13 pre-treatment effectively attenuated the cisplatin-induced ROS and superoxide anion generation, inhibited DNA damage, and suppressed the PARP cleavage and caspases activation. Further investigation revealed that apelin-13 blocked cisplatin-induced H9c2 cells apoptosis involving the regulation of MAPKs and PI3K/Akt signaling pathway. Importantly, apelin-13 co-treatment also significantly attenuated cisplatin-induced cardiotoxicity in vivo by inhibiting myocardial cells apoptosis and improving angiogenesis in mice heart. Taken together, our results suggest that the use of apelin-13 may be an effective strategy for antagonizing the cardiotoxicity-induced by platinum-based chemotherapy.

Soluble epoxide hydrolase inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, represses human aortic smooth muscle cell proliferation and migration by regulating cell death pathways via the mTOR signaling.

The soluble epoxide hydrolase (sEH) is a molecule necessary for the metabolism of endogenous constituents implicated in blood pressure regulation and vascular inflammation. Scientific evidences indicate that sEH inhibitors such as 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid (AUDA) could be a possible therapeutic option for cardiovascular diseases such as restenosis and atherosclerosis. However, the nature of the biological effects of AUDA still remains unclear. Herein, we intended to scrutinize the influence of AUDA on proliferation and migration of TNF-α-induced human aortic smooth muscle cells (HASMCs) and the underlying molecular mechanism. Pretreatment with AUDA (0.5-8 µM) dose-dependently inhibited TNF-α-induced proliferation of HASMCs as revealed by the MTT assay and the decreased expression of Cyclin D1 and ß-tubulin. Transwell analyses showed that AUDA equally suppressed TNF-α-induced migration of HASMCs. Moreover, AUDA induced the expression of apoptotic proteins (Caspase 3, PARP) and inhibited the expression of autophagy related markers (LC3-II and Beclin 1). More interestingly, AUDA inhibited TNF-α-induced phosphorylation of mTOR, the silencing of which abolished the inhibitory effects of AUDA on TNF-α-induced HASMCs. The present results point toward an inhibitory effect of AUDA on the proliferation and migration of TNF-α-induced HASMCs by regulation of cell death related signaling pathways via downregulation of the mTOR signaling. Thus, AUDA may be an important regulator of inflammation in the atherosclerotic lesion and a novel therapeutic drug for the treatment of atherosclerosis, restenosis and other cardiovascular diseases.

Long-term prognostic value of QRS score in patients with successfully recanalized coronary chronic total occlusion and construction of a predictive nomogram model.

BACKGROUND: Few studies have evaluated the prognostic value of QRS score in patients with coronary chronic total occlusion (CTO) after successful recanalization. METHODS: A total of 474 patients with successfully recanalized coronary CTO were finally included in our study and were followed up for 34.0±5.3months. They were divided into 3 groups: QRS score≥8, QRS score 4-7 and QRS score 0-3. The primary outcome was composite endpoint of major adverse cardiac and cerebral events (MACCEs). A predictive nomogram was established to predict prognosis for MACCEs, and the predictive accuracy of the nomogram was determined by concordance index. RESULTS: We found that QRS score correlated moderately with wall motion score index (WMSI) (r=0.551, p<0.001), left ventricular ejection fraction (LVEF) (r=-0.339, p<0.001) and coronary collateral circulation (CCC) (r=-0.569, p<0.001). During follow-up, patients with higher QRS score were observed to undergo poor prognosis. After multivariable adjustment, QRS score was still a significant independent predictor for MACCEs [(hazard ratio 1.28, 95% CI 1.18-1.39, p<0.001) in model 1,(hazard ratio 1.30, 95% CI 1.21-1.41, p<0.001) in mode2] and mortality[(hazard ratio 1.33, 95% CI 1.14-1.57, p<0.001) in model 1, (hazard ratio 1.49 , 95% CI 1.24-1.79, p<0.001) in model 2]. Moreover, the nomogram could more accurately predict 3-year MACCEs (c-index: 0.84). CONCLUSION: QRS score is a strong independent predictor of long-term prognosis in patients with coronary CTO successfully recancalized. The proposed nomograms can be used for the prediction of MACCE in this population.

Influence of chronic kidney disease on the outcome of patients with chronic total occlusion.

OBJECTIVE: Chronic kidney disease (CKD) predicted a poor prognosis in patients with coronary artery disease. There is a paucity of data on outcomes after revascularization in patients with chronic total occlusion (CTO) and CKD. This study aims to investigate the impact of CKD on the revascularization of CTO. METHODS: This study enrolled 1,092 CTO patients received treatments in our hospital between February 2009 and January 2014. Major adverse cardiac and cerebrovascular events (MACCE) and all-cause mortality were compared to evaluate medium- and long-term outcomes. Median follow-up was 39 months (interquartile range, 27-52 months). RESULT: CKD decreased cumulative MACCE-free survival rate (54.4 ± 6.2% vs. 70.9 ± 2.5%, P < 0.001) and cumulative survival rate (68.6 ± 6.3% vs. 90.5 ± 1.6%, P < 0.001). Revascularization was associated with better outcomes among patients with (MACCE-free survival rate: 64.8 ± 5.7% vs. 20.1 ± 15.3%, P = 0.009; survival rate 78.4 ± 5.6% vs. 38.7 ± 17.4%, P = 0.006) or without CKD (MACCE-free survival rate 73.9 ± 2.7% vs. 61.0 ± 5.4%, P = 0.001; survival rate 92.9 ± 1.5% vs. 83.8 ± 4.0%, P = 0.009). The benefit from revascularization was attenuated by CKD. Compared with percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) had similar cumulative survival rates among patients, whether with or without CKD, but was associated with a higher cumulative MACCE-free survival rate (80.5 ± 3.4% vs. 68.5 ± 4.0%, P = 0.017) among patients without CKD. CONCLUSION: CKD attenuated the benefit from revascularization for CTO. Moreover, CABG was not superior to PCI among CTO patients, but with a reduction in MACCE in patients without CKD.

Effect of calcium channels blockers and inhibitors of the renin-angiotensin system on renal outcomes and mortality in patients suffering from chronic kidney disease: systematic review and meta-analysis.

BACKGROUND: The renoprotective effect of inhibitors of renin-angiotensin system (RAS) has been identified through placebo-controlled trials. However, the effect of calcium-channel blockers (CCBs) on renal system is still controversial. Our current meta-analysis includes available evidences to compare the effect of dihydropyridine CCBs and ACEIs or ARBs on renal outcomes and mortality. We also further investigate whether CCBs can be used in combination with inhibitors of RAS to improve the prognosis of patients with chronic kidney disease (CKD). METHODS AND RESULTS: Electronic databases were searched up to July 2012, for clinical randomized controlled trials, assessing the effect of dihydropyridine CCBs on the incidence of end-stage renal disease (ESRD) and all-cause mortality in contrast to ACEIs or ARBs. Eight clinical trials were included containing 25,647 participants. ESRD showed significantly higher frequency with CCBs therapy compared with ACEIs or ARBs therapy, though blood pressure was decreased similarly in both groups in every trial (OR, 1.25; 95% CI, 1.05-1.48; p = 0.01). In contrast, there was no significant difference in the incidence of all-cause mortality between these two groups, though ACEIs or ARBs exhibited better renoprotective effect compared to CCBs (OR, 0.96; 95% CI, 0.89-1.03; p = 0.24). CONCLUSIONS: CCBs did not increase all-cause mortality incidence in patients with CKD though they displayed weaker renoprotective, compared to ACEIs or ARBs therapy. Our results suggest the combination of a CCB and an ACEI or ARB should be a preferable antihypertensive therapy in patients with CKD, considering their higher effect in decreasing blood pressure and fewer adverse metabolic problems caused.

Long-term outcome of intravascular ultrasound application in patients with moderate coronary lesions and grey-zone fractional flow reserve.

OBJECTIVE: This study aimed to assess the long-term outcome of intravascular ultrasound (IVUS) application in patients with a fractional flow reserve (FFR) of 0.75-0.80. BACKGROUND: Scientifically evaluating anatomical structures is vital because structure influences both physiological function and decision-making in moderate coronary lesions, especially for those with an FFR of 0.75-0.80. MATERIALS AND METHODS: Patients (n=128) were divided into three groups based on treatment: the drug control group (n=40), the IVUS-percutaneous coronary intervention (PCI) group (n=40) and the IVUS-drug group (n=48). A PCI was performed when a patient had a minimum lumen area less than 4 mm(2) and a plaque burden of 70% or greater. Major adverse clinical events were defined as cardiac death, nonfatal myocardial infarction, target vessel revascularization, including PCI or coronary artery bypass grafting, and unstable angina, all of which were also evaluated during follow-up. RESULTS: Kaplan-Meier curves indicated that the incidence of major adverse clinical events did not differ between the IVUS-PCI and IVUS-drug groups (5 vs. 6.3%, P=0.810), but the levels in both of these groups significantly decreased compared with the drug control group (5 vs. 22.5%, P=0.024, and 6.5 vs. 22.5%, P=0.026, respectively). CONCLUSION: The long-term outcome of the application of IVUS in patients with a grey-zone FFR of 0.75-0.80 was superior to that of patients who were treated only with drugs without IVUS measurement. Patients with a grey-zone FFR should receive an individualized treatment strategy according to their IVUS parameters. Patients with the same FFR values may require different treatment strategies.

Effect of Grape Polyphenols on Blood Pressure: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of grape polyphenols on blood pressure remains unclear, which we aimed to address via a meta-analysis study. METHODS: We conducted study trial searches in PubMed, Embase, and the Cochrane Library databases. Summary estimates of weighted mean differences and 95% confidence intervals were obtained by using fixed-effects models. Subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the international database of prospectively registered systematic reviews (registration number CRD42015019196). RESULTS: Ten studies were included in the present meta-analysis. Our results showed daily grape polyphenol intake could significantly reduce systolic blood pressure by 1.48 mmHg when compared to control subjects (12 comparisons; -1.48 [-2.79 to -0.16] mmHg; P = 0.03). Subgroup analyses indicated larger reduction was identified in the intake of low-dose of grape polyphenols (< 733 mg/day, median level of the included studies) or patients with metabolic syndrome. Contrarily, diastolic blood pressure was not significantly decreased in the grape polyphenols group as compared to controls. No significant heterogeneity or publication bias was detected in the meta-analysis of either systolic or diastolic blood pressure. CONCLUSIONS: Daily grape polyphenol intake can significantly reduce the systolic blood pressure in humans, although the reduction is modest when compared with anti-hypertensive medications. Larger, better designed trials, that specifically include hypertensive subjects, are required to verify our results in the future.

Short-term clinical outcomes after hybrid coronary revascularization versus off-pump coronary artery bypass for the treatment of multivessel or left main coronary artery disease: a meta-analysis.

BACKGROUND: Hybrid coronary revascularization (HCR) and off-pump coronary artery bypass grafting (OPCABG) are both feasible, less invasive techniques for coronary revascularization. Although both techniques utilize the left internal mammary artery to left anterior descending artery graft, HCR uses drug-eluting stents instead of saphenous vein bypass. It remains unclear whether HCR is equal to, better or worse than OPCABG. METHODS AND RESULTS: A meta-analysis was carried out using a random-effects model. Seven observational studies were included. There was no significant difference either in in-hospital mortality [relative risk (RR) 0.57, 95% confidence interval (CI) 0.13-2.59, P=0.47] or in the MACCE rate (RR 0.63, 95% CI 0.24-1.64, P=0.34) between the HCR group and the OPCABG group. A significant difference was observed between the two groups in the length of hospitalization (RR 0.55, 95% CI 0.13-0.97, P=0.01), length of ICU stay (RR 0.45, 95% CI 0.10-0.80, P<0.05), intubation time (RR 0.48, 95% CI 0.13-0.84, P<0.01), need for red blood transfusion (RR 0.67, 95% CI 0.56-0.82, P<0.001), and total in-hospital costs (RR 0.90, 95% CI 0.39-1.42, P<0.01). CONCLUSION: Compared with OPCABG, HCR did not improve early survival but decreased the length of hospitalization, length of ICU stay, intubation time, and need for red blood transfusion, and increased total in-hospitalcosts.

The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

BACKGROUND: The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). METHODS: Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. RESULTS: Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. CONCLUSIONS: Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

The effect of trimetazidine on cardiac function in diabetic patients with idiopathic dilated cardiomyopathy.

AIMS: Trimetazidine is an anti-ischemic metabolic agent which improves myocardial glucose utilization. Whether it may improve cardiac function and physical tolerance in diabetic patients with idiopathic dilated cardiomyopathy is still not confirmed. In this study we have investigated the effectiveness of trimetazidine in these patients. MAIN METHODS: Volunteers with diabetes and idiopathic dilated cardiomyopathy were recruited for participation in this study. Patients were randomized into two groups. One group received trimetazidine (20mg, t.i.d.) for 6 months (n=40), while another group received a placebo during the same period (n=40). All patients received an echocardiographic examination, 6-minute walk test and an inflammation biochemical analysis (C reactive protein) at baseline and after 6 months of treatment. KEY FINDINGS: No significant adverse events or changes in clinical or biochemical parameters were detected through the study. After 6 months, TMZ-treated patients had a significant improvement in systolic function as compared with control patients associated with an increased ratio of E/A. C reactive protein concentrations remained stable throughout the study in trimetazidine group at baseline and at the 6 month on follow up. In comparison, it increased significantly in the control group at the 6-month follow up. The NT-pro BNP levels did not change in the control group, whereas they significantly decreased in the trimetazidine group. The physical activity tolerance level improved in the trimetazidine group compared to the control group. SIGNIFICANCE: Trimetazidine treatment was associated with a significant improvement of cardiac function and physical tolerance. Results also suggested that the inflammatory response was decreased in trimetazidine group as compared with control patients.

[Cardiac metallothionein overexpression improves cardiac contractile function and attenuates oxidative stress in lipopolysaccharide-treated mice].

OBJECTIVE: This study was designed to examine the impact of the antioxidant metallothionein (MT) on cardiac contractile, intracellular Ca(2+) function and oxidative stress in lipopolysaccharide (LPS)-treated mice. METHODS: Weight and age matched adult male FVB and cardiac-specific MT-overexpressing transgenic mice were injected intraperitoneally with 4 mg/kg Escherichia Coli LPS dissolved in sterile saline or an equivalent volume of pathogen-free saline (control groups). Six hours following LPS or saline injection, cardiac geometry and function were evaluated in anesthetized mice using the 2-D guided M-mode echocardiography. Mechanical and intracellular Ca(2+) properties were examined in hearts. Cell shortening and relengthening were assessed using the following indices: peak shortening (PS)-indicative of the amplitude a cell can shorten during contraction; maximal velocities of cell shortening and relengthening (± dl/dt)-indicative of peak ventricular contractility; time-to-PS (TPS)-indicative of systolic duration; time-to-90% relengthening (TR(90))-indicative of diastolic duration (90% rather 100% relengthening was used to avoid noisy signal at baseline concentration). The 360 nm excitation scan was repeated at the end of the protocol and qualitative changes in intracellular Ca(2+) concentration were inferred from the ratio of fura-2 fluorescence intensity (FFI) at two wavelengths (360/380). Fluorescence decay time was measured as an indicator of the intracellular Ca(2+) clearing rate. Glutathione/glutathione disulfide ratio and ROS generation were detected as the markers of oxidative stress. RESULTS: Heart rate was increased while EF was reduced in LPS-FVB mice and heart rate was reduced and EF increased in MT-LPS transgenic mice [(528 ± 72) beats/min vs (557 ± 69) beats/min, (66 ± 14)% vs (42 ± 10)%, P < 0.05]. Cardiomyocytes from the LPS treated FVB mice displayed significantly reduced peak shortening (PS) and maximal velocity of shortening/relengthening (±dl/dt) associated with prolonged time-to-90% relengthening (TR(90)), these effects were attenuated in cardiomyocytes from the MT-LPS mice [PS(5 ± 1.1)% vs (7.2 ± 0.8)%, dl/dt(160 ± 15) µm/s vs (212 ± 36) µm/s, -dl/dt (175 ± 32) µm/s vs (208 ± 29) µm/s, TR(90) (0.24 ± 0.03)s vs (0.19 ± 0.02)s, P < 0.05]. LPS treated mice showed significantly reduced peak intracellular Ca(2+) and electrically-stimulated rise in intracellular Ca(2+) as well as prolonged intracellular Ca(2+) decay rate without affecting the basal intracellular Ca(2+) levels, again, these effects were significantly attenuated in MT-LPS transgenic mice. Metallothionein overexpression also ablated oxidative stress [reduced ROS generation and increased glutathione/glutathione disulfide ratio, ROS (0.35 ± 0.08) A/µg protein vs (0.24 ± 0.03) A/µg protein]. GSH/GSSG 2.1 ± 0.2 vs 2.6 ± 0.4, P < 0.05. CONCLUSION: MT overexpression improved cardiac function and ablated oxidative stress in LPS treated mice.

ACE2 overexpression inhibits angiotensin II-induced monocyte chemoattractant protein-1 expression in macrophages.

BACKGROUND: The discovery of angiotensin-converting enzyme 2 (ACE2) has shed light on the potential therapy for cardiovascular disease, owing to its key role in the formation of vasoprotective peptide angiotensin (Ang 1-7) from angiotensin (Ang) II. The aim of this study was to evaluate whether ACE2 overexpression could protect human monocyte cell line (THP-1) macrophages from angiotensin II-induced monocyte chemoattractant protein-1 (MCP-1) formation. METHODS: A truncated form of mouse ACE2 (mACE2) was cloned into adenovirus vector (Ad-ACE2) and transfected into THP-1. We examined expression of MCP-1 by administration of a selected Ang (1-7) antagonist (A779) to show the effect of ACE2 overexpression on MCP-1 level induced by AngII. RESULTS: AngII-induced MCP-1 expression increased obviously at 24 h and at the concentration of 10(-6) M. Transduction of THP-1 with Ad-ACE2 resulted in a viral increase in ACE2 activity. This was associated with a significant attenuation of AngII-induced MCP-1 production by 39.6+/-4.0% in THP-1 (mean+/-SEM, n=3). Moreover, expression of MCP-1 increased by 35.1+/-4.2% in Ad-ACE2 transfected THP-1 after incubation with Ang II and A779 compared to that with AngII alone. Collectively, these results indicated that ACE2 overexpression in the THP-1 attenuates AngII-induced MCP-1 production and that this reduction is likely mediated by increased Ang (1-7) level. CONCLUSIONS: ACE2 overexpression may provide a new therapeutic strategy for atherosclerosis by inhibiting MCP-1 production induced by AngII.

[Effect of Xuezhikang on cardiac function, serum C-reactive protein and blood lipid in patients with chronic heart failure].

OBJECTIVE: To evaluate the effect of Xuezhikang (XZK) on cardiac function and serum C-reactive protein (CRP) in patients with chronic heart failure (CHF). METHODS: Sixty-eight CHF patients were randomly assigned to two groups, the control group (30 cases) treated with angiotensin converting enzyme inhibitor, beta-receptor inhibitor, digoxin and diuretic, and the treated group (38 cases) with the above treatment plus XZK for six months. The changes of cardiac function and serum CRP level were measured by echocardiography and enzyme-linked immunosorbent assay (ELISA) respectively before and after treatment. RESULTS: Compared with those before treatment, the NYHA cardiac function grade, the left ventricular dimension end diastole (LVDd), and the left ventricular dimension end systole (LVDs) decreased significantly (P < 0.05), and the ejection fraction (EF) and E/A ratio increased significantly in both groups after treatment (P < 0.05) , however, the decrement or increment was more significant in the treated group than that in the control group respectively (P < 0.05); the serum CRP level decreased significantly in the treated group after treatment and showed a level obviously lower than that in the control group (P < 0.05), which changed insignificantly after treatment. CONCLUSION: Xuezhikang could improve cardiac function and decrease serum CRP level at the same time.

[Association between serum cardiac troponin I and myocardial remodeling in patients with chronic heart failure].

OBJECTIVE: To investigate the association between serum cardiac troponin I (cTnI) and cardiac function/structure in patients with chronic heart failure. METHODS: One hundred and twenty patients with decompensated chronic heart failure were included. The patients were divided into cTnI normal group (cTnIn; n = 80) and cTnI elevated group (cTnIe; n = 40). Systolic dimension of the left atrium (LAd), the maximal width of the left ventricle (LVd), the thickness of the interventricular septum (IVS) and posterior wall (LVPW) during diastole, left ventricle ejection fraction (LVEF), E and A wave velocities ratio (E/A) were determined. Bivariate correlation analysis was applied to show the correlation of serum cTnI level with above indices. Partial correlation analysis was performed followed by multivariate logistic regression. RESULTS: LAd and LVd dimensions were significantly higher (P < 0.05), IVS, LVPW, LVEF and E/A ratio were significantly lower (P < 0.05) in cTnIe group than in cTnIn group. Moreover, serum cTnI was positively correlated with LAd, LVd, and inversely correlated with IVS, LVPW, LVEF and E/A ratio (P < 0.05). The correlation persistent after adjusting with sex, history of heart failure, NYHA functional class and treatment. In multivariate modeling, cTnI was positively associated with LAd, LVd and the history of heart failure, and negatively related with the treatment with angiotensin-converting enzyme inhibitor. CONCLUSION: Serum cTnI correlated with cardiac structure and function. Intensively serum cTnI monitoring and suitable therapy strategy may be helpful to attenuate the cardiac remodeling in patients with chronic heart failure.

[Effects of cordyceps sinensis alcohol extractive on serum interferon-gamma level and splenic T lymphocyte subset in mice with viral myocarditis].

AIM: To investigate the effects of early application of cordyceps sinensis alcohol extractive (CSAE) on myocardial injury, level of serum IFN-gamma and splenic T lymphocyte subset in murine viral myocarditis (VMC). METHODS: 100 male BALB/c mice were divided randomly into control group (CG), infectious group (IG) and CSAE therapy group (CTG). Mice in IG and CTG were infected with Coxsackie virus B3 (CVB3). The 14-day survival rates and myocardial histopathology were observed. Serum IFN-gamma level was detected by ELISA and splenic CD3+, CD4+, CD8+ T lymphocytes were detected by flow cytometry. RESULTS: Serum IFN-gamma level and the percentage of splenic T lymphocyte subset in IG were decreased significantly, and CD4+/CD8+ T cell ratio increased significantly as compared with those of CG. Myocardial lesions in CIG were attenuated, while the 14-day survival of mice 85% (vs IG 55%, P<0.05), serum IFN-gamma and the percentage of splenic CD3+, CD8+ T lymphocytes in CTG were significantly higher than those in IG. There were no significant differences of the percentage of T lymphocyte subset and CD4+/CD8+ T cell ratio between CTG and CG. CONCLUSION: CSAE plays an important protective role against viral-induced murine myocarditis by inducing IFN-gamma and regulating T lymphocyte.