Minzhou Zhang

Phytoestrogen, tanshinone IIA diminishes collagen deposition and stimulates new elastogenesis in cultures of human cardiac fibroblasts

It has been previously reported that oral or intra-peritoneal administration of tanshinone IIA can alleviate the ventricular hypertrophy and fibrosis that develops in rats after experimental cardiac infarction. Our present studies, performed on cultures of human cardiac fibroblasts, investigated the mechanism by which tanshinone IIA produces these beneficial effects. We found that treatment of cardiac fibroblasts with 0.1-10µM tanshinone IIA significantly inhibited their deposition of collagen I, while enhancing production of new elastic fibers. Moreover, both anti-collagenogenic and pro-elastogenic effects of tanshinone IIA occurred only after selective activation of the G protein-coupled estrogen receptor (GPER). This subsequently leads to initiation of the PKA/CREB phosphorylation pathway that inversely modulated transcription of collagen I and elastin genes. Interestingly, treatment of human cardiac fibroblasts with tanshinone IIA additionally up-regulated the production of the 67-kDa elastin binding protein, which facilitates tropoelastin secretion, and increased synthesis of lysyl oxidase, catalyzing cross-linkings of tropoelastin. Moreover, tanshinone IIA also caused up-regulation in the synthesis of collagenolytic MMP-1, but down-regulated levels of elastolytic MMP-2 and MMP-9. In summary, our data validate a novel mechanism in which tanshinone IIA, interacting with a non-classic estrogen receptor, maintains the proper balance between the net deposition of collagen and elastin, allowing for optimal durability and resiliency of the newly deposited matrix.

Tanshinone IIA inhibits angiotensin II induced extracellular matrix remodeling in human cardiac fibroblasts — Implications for treatment of pathologic cardiac remodeling

Article history: Received 26 July 2015 Accepted 21 August 2015 Available online 29 August 2015 Smad proteins [7]. Moreover, other evidence has suggested that Ang II has also been suggested to signal independently of Smads to promote fibrosis. Ang II activates downstream mitogen-activated protein kinase (MAPK) signaling pathways, including extracellular-regulated kinase (ERK) and p38. However, the activated pathways appear to context and cell-specific [8]. Although Ang II is a well-recognized positive regulator of fibroblasts

Sodium tanshinone IIA sulfonate for reduction of periprocedural myocardial injury during percutaneous coronary intervention (STAMP trial): Rationale and design

a Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, China b Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China c Chinese Medicine Research Institute, Tianjin University of Chinese Medicine, Tianjin 300193, China d Physiology & Experimental Medicine, Hospital for Sick Children, Toronto M5G 0A4, Canada

Mechanisms of Chinese Medicine Xinmailong’s protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes

Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML’s effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3β and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3β, subsequently inhibiting protein expression of GATA4 in nucleus (P < 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3β, and GATA4 signaling pathway.

Prognostic value of non-high-density lipoprotein cholesterol for mortality in patients with coronary heart disease: A systematic review and meta-analysis.

BACKGROUND AND AIMS Recent studies have indicated the predictive value of non-high-density lipoprotein cholesterol (non-HDL-C) for mortality in patients without coronary heart disease (CHD). However, its independent prognostic value on patients with CHD has yet been explored. The purpose of this study was to investigate whether non-HDL-C could predict long-term mortality in patients with CHD. METHODS A comprehensive search for literature was performed in several database, including Medline, the Cochrane library, Embase and 3 Chinese databases. Studies were included if they reported risk estimation of mortality on CHD patients. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated to assess the association. We performed sensitivity analyses to explore the potential sources of heterogeneity. Statistical analyses were carried out by Stata 12.0. RESULTS After screening 533 studies, 6 trials (follow up range from 18 to 148months) enrolling 11,057 CHD patients were included. CHD patients with high non-HDL-C level at baseline was associated with higher risk of mortality (RR: 1.24, 95%CI: 1.05-1.46, p: 0.011). Results from continuous analyze showed that each 10mg/dl increase in non-HDL-C was associated with an increased risk of mortality in CHD patients (RR: 1.13, 95%CI: 1.06-1.21, p<0.001). CONCLUSION The increased levels of non-HDL-C were significantly associated with an increased risk of mortality on CHD patients. Baseline non-HDL-C levels might be a practical predictor of long-term death in patients with CHD.

Salvianolate reduces murine myocardial ischemia and reperfusion injury via ERK1/2 signaling pathways in vivo

ObjectiveTo analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.MethodsMyocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.ResultsThere were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).ConclusionSalvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

Background Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF. Methods We created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg-1•day-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function in vivo. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4. Results SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC surgery. Conclusions Our data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.

Strong correlation between lung ultrasound and chest computerized tomography imaging for the detection of acute lung injury/acute respiratory distress syndrome in rats.

BACKGROUND Lung ultrasound (LUS) is a clinical imaging technique for diagnosing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In humans and several large animals, LUS demonstrates similar specificity and sensitivity to computerized tomography (CT) scanning. Current study evaluated the degree of agreement between LUS and CT imaging in characterizing ALI/ARDS in rats. METHODS Thirty male Sprague-Dawley rats were imaged by LUS before randomization into three groups to receive intratracheal saline, 3 or 6 mg/kg LPS respectively (n=10). LUS and CT imaging was conducted 2 hours after instillation. Cross table analyses and kappa statistics were used to determine agreement levels between LUS and CT assessments of lung condition. RESULTS Before instillation, rats presented with a largely A-pattern in LUS images, however, a significantly increase B-lines were observed in all groups after instillation and showed dose response to LPS or to saline. One rat treated with 6 mg/kg lipopolysaccharide (LPS) presented with lung consolidation. The agreement between the LUS and the CT in detecting the main characteristics of ALI/ARDS in rat was strong (r=0.758, P<0.01, k=0.737). CONCLUSIONS In conclusion, LUS detects ALI/ARDS with high agreement with micro PET/CT scanning in a rat model, suggesting that LUS represents a positive refinement in rat ALI/ARDS disease models.

Relation of C-reactive protein and new-onset atrial fibrillation in patients with acute myocardial infarction: A systematic review and meta-analysis

a Department of Cardiology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing 400021, China b Division of Chest Pain Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510120, China c The 2nd Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China d Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, China

Protect effects of Danlou Tablet (丹蒌片) against murine myocardial ischemia and reperfusion injury in vivo

ObjectiveTo observe the in vivo effect of Danlou Tablet (丹蒌片, DLT) on myocardial ischemia and reperfusion (I/R) injury.MethodsDLT effects were evaluated in mouse heart preparation using 30-min coronary occlusion followed by 24-h reperfusion and compared among sham group (n=6), I/R group (n=8), IPC group (ischemia preconditioning, n=6) and DLT group (I/R with DLT pretreatment for 3 days, 750 mg•kg-1•day-1, n=8). The effects of DLT were characterized in infarction size (IS) compared with risk region (RR) and left ventricle using the Evans blue/triphenyltetrazolium chloride double dye staining method in vivo. Furthermore, the dose-dependent effect of DLT on I/R injury was evaluated by double staining method. Five different concentrations of DLT (0.625, 1.25, 2.5, 5 and 10 g•kg-1•day-1) were chosen in this study, and dose-response curve of DLT was obtained on these data.ResultsThe ratio of IS to left ventricle was significantly smaller in the DLT and IPC groups than the I/R group (P<0.05 or P<0.01), the ratio of IS to RR was also reduced in the DLT and IPC groups (P<0.01), while there were no differences in RR among the four groups (P>0.05). Experiments showed incidence of arrhythmias was reduced in the DLT group (P<0.01). Furthermore, DLT produced a dose-dependent inhibitory effect with a half maximal inhibitory concentration of 1.225 g•kg-1•day-1.ConclusionsOur research concluded that DLT was effective in reducing I/R injury in mice, and provided experimental supports for the clinical use of DLT.