Mingqiang Fu

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis.

BACKGROUND To systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus. METHODS We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months. RESULTS 7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83-1.02, p=0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85-1.06; p=0.33), cardiovascular mortality (0.95, 95% CI 0.71-1.27; p=0.71), stroke (0.83, 95% CI 0.63-1.10; p=0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65-1.11; p=0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70-8.61; p=0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men. CONCLUSIONS In patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.

High density lipoprotein protects mesenchymal stem cells from oxidative stress-induced apoptosis via activation of the PI3K/Akt pathway and suppression of reactive oxygen species.

The therapeutic effect of transplantation of mesenchymal stem cells (MSCs) in myocardial infarction (MI) appears to be limited by poor cell viability in the injured tissue, which is a consequence of oxidative stress and pro-apoptotic factors. High density lipoprotein (HDL) reverses cholesterol transport and has anti-oxidative and anti-apoptotic properties. We, therefore, investigated whether HDL could protect MSCs from oxidative stress-induced apoptosis. MSCs derived from the bone marrow of rats were pre-incubated with or without HDL, and then were exposed to hydrogen peroxide (H2O2) in vitro, or were transplanted into experimentally infarcted hearts of rats in vivo. Pre-incubation of MSCs with HDL increased cell viability, reduced apoptotic indices and resulted in parallel decreases in reactive oxygen species (ROS) in comparison with control MSCs. Each of the beneficial effects of HDL on MSCs was attenuated by inhibiting the PI3K/Akt pathway. Preconditioning with HDL resulted in higher MSC survival rates, improved cardiac remodeling and better myocardial function than in the MSC control group. Collectively, these results suggest that HDL may protect against H2O2-induced apoptosis in MSCs through activation of a PI3K/Akt pathway, and by suppressing the production of ROS.

Efficacy of ACE inhibitors in chronic heart failure with preserved ejection fraction — A meta analysis of 7 prospective clinical studies

BACKGROUND The effect of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction remains controversial. AIMS To assess the impact of ACE inhibitors on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction. METHODS AND RESULTS Seven prospective studies evaluating the effect of ACE inhibitors compared to placebo or other classes of drugs, such as monotherapy or first-line therapy, on the prognosis of chronic heart failure patients with preserved left ventricular ejection fraction were included. A total of 2554 patients (mean age: 75.1 years, female: 58%) were recruited with an average follow up of 20.9 months. The primary etiology of heart failure with preserved ejection fraction was ischemic heart disease (33.7%), hypertension (69.1%) and diabetes mellitus (25.8%). Our results demonstrated that ACE inhibitors significantly reduced all-cause mortality (odds ratio, OR = 0.52; 95% Confidence Interval (CI), 0.41 to 0.64; P<0.01). Furthermore, ACE inhibitors were able to reduce heart failure related rehospitalization or treatment over 20.9 months (p<0.05) in a subgroup of patients aged over 75 years. However, death due to worsening of heart failure, heart failure related rehospitalization and any-cause readmission were not affected (OR = 0.88; 95% CI: 0.66 to 1.17; P = 0.37 for death due to worsening of heart failure; OR = 0.81; 95% CI: 0.63 to 1.05; P = 0.11 for heart failure related rehospitalization and OR = 0.88; 95% CI: 0.68 to 1.14; P = 0.33 for any-cause readmission, respectively). CONCLUSIONS In patients with chronic heart failure with preserved ejection fraction, ACE inhibitors reduced all-cause mortality without affecting mortality due to heart failure and any-cause rehospitalization.

Efficacy and safety of intracoronary autologous bone marrow-derived cell transplantation in patients with acute myocardial infarction: insights from randomized controlled trials with 12 or more months follow-up.

Until now there was no systematic review concerning the chronic effects of intracoronary bone marrow‐derived cell (BMC) transplantation in patients with acute myocardial infarction (MI).

Effects of intensive glucose control on incidence of cardiovascular events in patients with type 2 diabetes: A meta-analysis

Abstract Background. The effects of intensive glucose control over conventional glucose control on cardiovascular outcomes of patients with type 2 diabetes remain uncertain. Methods. We searched MEDLINE, EMBASE, and the Cochrane database to identify randomized controlled trials that compared the effects of intensive glucose control and conventional glucose control, on cardiovascular events in patients with type 2 diabetes. Results. Seven trials involving 34,144 participants with type 2 diabetes were included. Intensive glucose control significantly reduced major cardiovascular events by 10% (relative risk (RR) 0.90, 95% CI 0.85–0.96; P = 0.0006), and non-fatal myocardial infarction by 16% (0.84, 95% CI 0.76–0.93; P = 0.0006) at the expense of increased incidence of severe hypoglycemia (2.30, 95% CI 1.74–3.03; P < 0.00001), while all-cause mortality, cardiovascular death, non-fatal stroke, and heart failure were similar between the two groups. Subgroup analyses showed that patients with longer follow-up duration, shorter diabetic duration, less glycosylated hemoglobin (HbA1c) reduction, higher HbA1c concentration at follow-up, and lower base-line HbA1c benefited more from intensive glucose control. Conclusion. An intensive glucose control strategy can effectively reduce the risk of major cardiovascular events but at the expense of a significantly increased risk of severe hypoglycemia in patients with type 2 diabetes.

High density lipoprotein cholesterol promotes the proliferation of bone-derived mesenchymal stem cells via binding scavenger receptor-B type I and activation of PI3K/Akt, MAPK/ERK1/2 pathways

High-density lipoprotein (HDL) possesses protective properties in cardiovascular diseases. However, the effect of HDL on the mesenchymal stem cells (MSCs), which could be mobilized to the damaged myocardial tissue, has not been well elucidated yet. In the current study, we investigated the effect of HDL on the proliferation of MSCs so as to reveal its molecular mechanisms. MSCs derived from rats were treated with HDL in different concentrations and for different periods. The proliferation of MSCs was measured with MTT and BrdU cell proliferation assay. The phosphorylation of Akt, ERK1/2 and the expression of p21 were evaluated by Western blotting. After the activity of respective pathways was down-regulated by the specific inhibitor and the gene of scavenger receptor-B type I (SR-BI) was knocked down by RNA interference, BrdU assay was performed to examine this effect of HDL on MSCs. We found that the proliferation of MSCs induced by HDL, in a time- and concentration-dependent manner, was the phosphorylation of Akt- and ERK1/2-dependent, which was significantly attenuated by the specific inhibitor to respective pathways. Moreover, MAPK/ERK1/2 pathway exerted a more dominating effect on this process. SR-BI contributed to HDL-induced proliferation of MSCs, which was effectively abolished by the silencing of SR-BI. The results suggested that HDL was capable of improving MSCs proliferation, in which MAPK/ERK1/2 and PI3K/Akt pathways involved and SR-BI played a critical role as well.

miR-210 over-expression enhances mesenchymal stem cell survival in an oxidative stress environment through antioxidation and c-Met pathway activation

AbstractmicroRNA-210 (miR-210) has generally been reported to be associated with cell survival under hypoxia. However, there are few data regarding the role of miR-210 in the survival of mesenchymal stem cells (MSCs) under oxidative stress conditions. Thus, we sought to investigate whether miR-210 over-expression could protect MSCs against oxidative stress injury and what the primary mechanisms involved are. The results showed that over-expression of miR-210 significantly reduced the apoptosis of MSCs under oxidative stress, accompanied by obvious increases in cell viability and superoxide dismutase activity and remarkable decreases in malonaldehyde content and reactive oxygen species production, resulting in a noticeable reduction of apoptotic indices when compared with the control. Moreover, the above beneficial effects of miR-210 could be significantly reduced by c-Met pathway repression. Collectively, these results showed that miR-210 over-expression improved MSC survival under oxidative stress through antioxidation and c-Met pathway activation, indicating the potential development of a novel approach to enhance the efficacy of MSC-based therapy for injured myocardium.

Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study

BackgroundAdiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography.ResultsThe results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E′ (correlation coefficient (r) = −0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and −0.626 for E/E′, p = 0.002, respectively) while positively correlated with E/A and E′/A′ (r = 0.683 for E/A, p = 0.001, 0.671 for E′/A′, p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found.ConclusionAdiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.

Panax quinquefolium saponins inhibited immune maturation of human monocyte-derived dendritic cells via blocking nuclear factor-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE Panax quinquefolium saponins (PQS), a water-soluble antioxidant extracted from a natural herb, radix panacis quinquefolii (American Ginseng), has yielded encouraging results in the treatment of atherosclerotic diseases. However, the underlying mechanisms remain unclear. Here, we tested the hypothesis that the anti-atherosclerotic effect of PQS might be mediated by suppressing human monocyte-derived dendritic cells (DCs) maturation. MATERIALS AND METHODS DCs were derived by incubating purified human monocytes with granulocyte macrophage colony stimulating factor (GM-CSF) and IL-4. DCs were pre-incubated with or without PQS and stimulated by oxidized low density lipoprotein (ox-LDL). Expression of DCs membrane molecules (CD40, CD86, CD1a, HLA-DR) and endocytotic ability were analyzed by FACS, cytokines (IL-12 and TNF-α) were measured by ELISA. Nuclear factor (NF)-κB signaling pathway was determined by Western blotting, and RT-PCR. NF-κB activation was quantified by ELISA. RESULTS PQS reduced ox-LDL induced immunophenotypic expressions (CD40, CD1a, CD86, and HLA-DR) and cytokine secretions (IL-12 and TNF-α), and improved endocytotic ability of DCs. These above phenomena were accompanied by decreased protein expression and binding activity of nuclear localized c-Rel subunit. CONCLUSIONS Our study suggested that PQS inhibited ox-LDL induced immune maturation of DCs in vitro, which might be in part mediated by NF-κB signal transduction pathway.

Qiliqiangxin inhibits angiotensin II-induced transdifferentiation of rat cardiac fibroblasts through suppressing interleukin-6

Qiliqiangxin (QL), a traditional Chinese medicine, had long been used to treat chronic heart failure. Recent studies revealed that differentiation of cardiac fibroblasts (CFs) into myofibroblasts played an important role in cardiac remodelling and development of heart failure, however, little was known about the underlying mechanism and whether QL treatment being involved. This study aimed to investigate the effects of QL on angiotensin II (AngII)‐induced CFs transdifferentiation. Study was performed on in vitro cultured CFs from Sprague–Dawley rats. CFs differentiation was induced by AngII, which was attenuated by QL through reducing transforming growth factor‐β1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA). Our data showed that AngII‐induced IL‐6 mRNA as well as typeI and typeIII collagens were reduced by QL. IL‐6 deficiency could suppress TGF‐β1 and α‐SMA, and both IL‐6 siRNA and QL‐mediated such effect was reversed by foresed expression of recombined IL‐6. Increase in actin stress fibres reflected the process of CFs differentiation, we found stress fibres were enhanced after AngII stimulation, which was attenuated by pre‐treating CFs with QL or IL‐6 siRNA, and re‐enhanced after rIL‐6 treatment. Importantly, we showed that calcineurin‐dependent NFAT3 nuclear translocation was essential to AngII‐mediated IL‐6 transcription, QL mimicked the effect of FK506, the calcineurin inhibitor, on suppression of IL‐6 expression and stress fibres formation. Collectively, our data demonstrated the negative regulation of CFs differentiation by QL through an IL‐6 transcriptional mechanism that depends on inhibition of calcineurin/NFAT3 signalling.