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1.
Chin J Integr Med ; 29(2): 108-118, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36327050

ABSTRACT

OBJECTIVE: To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent. METHODS: VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models. RESULTS: SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG. CONCLUSION: SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.


Subject(s)
Arrhythmias, Cardiac , Calcium , Animals , Rabbits , Mice , Computer Simulation , Electrocardiography
2.
Biochem Res Int ; 2022: 5498023, 2022.
Article in English | MEDLINE | ID: mdl-36405392

ABSTRACT

Heart failure (HF) affects millions of patients in the world. Shexiang Baoxin Pills (SXB) are extensively applied to treat coronary artery diseases and HF in Chinese hospitals. However, there are still no explanations for why SXB protects against HF. To assess the protective role, we created the HF model in rats by isoproterenol (ISO) subcutaneous injection, 85 milligrams per kilogram body weight for seven days. Four groups were implemented: CON (control), ISO (HF disease group), CAP (captopril, positive drug treatment), and SXB groups. Echocardiography was used to evaluate rats' HF in vivo. The human CaV1.2 (hCaV1.2) channel currents were detected in tsA-201 cells by patch clamp technique. Five different concentrations of SXB (5, 10, 30, 50, and 100 mg/L) were chosen in this study. The results showed that SXB increased cardiac systolic function and inhibited rats' cardiac hypertrophy and myocardial fibrosis induced by ISO. Subsequently, it was found that SXB was inhibited by the peak amplitudes of hCaV1.2 channel current (P < 0.01). The SXB half inhibitory dosage was 9.09 mg/L. The steady-state activation curve was 22.8 mV depolarization shifted; while the inactivation curve and the recovery from inactivation were not affected significantly. In conclusion, these results indicated that SXB inhibited ISO-induced HF in rats and inhibited the hCaV1.2 channel current. The present study paved the way for SXB to protect itself from HF.

3.
Chin J Integr Med ; 26(8): 583-590, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32524394

ABSTRACT

OBJECTIVE: To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills (, SXJ) on myocardial ischemia and reperfusion (I/R) injury. METHODS: Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion, the mice were then divided into the sham group (n=7), the I/R group (n=13), the tirofiban group (TIR, positive drug treatment, n=9), and the SXJ group (n=11). Infarct size (IS), risk region (RR), and left ventricle (LV) were analyzed with double staining methods. In addition, H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro. The phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2), protein kinase B (AKT), glycogen synthase kinase-3ß (GSK3ß), and protein expression of GATA4 in nucleus were detected with Western blot assay. RESULTS: The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group (SXJ, 22.4% ±6.6%; TIR, 20.8%±3.3%; vs. I/R, 35.4%±3.7%, P<0.05, respectively). In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3ß and nuclear expression of GATA4. CONCLUSION: SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3ß and GATA4 signaling pathways.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Myocardial Reperfusion Injury/drug therapy , Animals , Cell Line , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Myocytes, Cardiac , Rats, Sprague-Dawley
4.
J Ethnopharmacol ; 253: 112660, 2020 May 10.
Article in English | MEDLINE | ID: mdl-32061912

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac hypertrophy is a key pathologic process in heart failure. Songling Xuemaikang Capsule (SXC), is a formulae of Chinese Medicine commonly used in China to treat hypertension and heart failure. However, its mechanism of effects on cardiac hypertrophy is still unclear. AIM OF THE STUDY: The aims of the present study were to investigate the cardio-protection roles and detailed mechanisms of SXC on cardiac hypertrophy in vivo and in vitro. MATERIALS AND METHODS: A rat model of cardiac hypertrophy was constructed by isoproterenol (ISO) intraperitoneal injection (i.p), 10 mg/kg/day for 3 days, and 4 groups were compared: CON (n = 8), ISO (n = 8), MET (metoprolol, positive drug treatment, n = 7), and SXC (SXC treatment, n = 6). Cardiac structure and function were evaluated with echocardiography in vivo. Dose-dependent curve was obtained with SXC different concentrations. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, p38, JNK, AKT, and protein expression of CaN, CaMKIIδ, GATA4 were detected with Western blot test. RESULTS: The results showed that SXC reduced diastolic thickness of left ventricular posterior wall, while did not change ejection fraction and fraction shortening significantly (P > 0.05). SXC inhibit ISO-induced cardiac hypertrophy dose-dependently with 50% inhibiting concentration (IC50) is 0.504 g/kg/day. Moreover, SXC inhibited the protein expression of CaMKIIδ, and the phosphorylation of ERK1/2, so inhibiting protein expression of GATA4 in nucleus, and brain natriuretic peptide in serum (P < 0.001). CONCLUSION: The mechanism of SXC in the treatment of heart diseases involves SXC dose-dependently inhibited the ISO-induced cardiac hypertrophy via inhibiting CaMKIIδ and ERK1/2/GATA4 signaling pathway.


Subject(s)
Cardiomegaly/drug therapy , Cardiotonic Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Animals , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Capsules , Cardiomegaly/chemically induced , Cardiomegaly/metabolism , Cardiomegaly/pathology , Cardiotonic Agents/chemistry , Cardiotonic Agents/pharmacology , Cell Line , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Isoproterenol , MAP Kinase Signaling System/drug effects , Male , Myocardium/metabolism , Myocardium/pathology , Phytochemicals/analysis , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Rats, Sprague-Dawley
5.
Chin J Integr Med ; 24(8): 613-620, 2018 Aug.
Article in English | MEDLINE | ID: mdl-27048409

ABSTRACT

OBJECTIVE: To observe the in vivo effect of Danlou Tablet (, DLT) on myocardial ischemia and reperfusion (I/R) injury. METHODS: DLT 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. RESULTS: The 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. CONCLUSIONS: Our research concluded that DLT was effective in reducing I/R injury in mice, and provided experimental supports for the clinical use of DLT.


Subject(s)
Cardiotonic Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Myocardial Reperfusion Injury/drug therapy , Animals , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/pathology , Arrhythmias, Cardiac/physiopathology , Body Temperature/drug effects , Cardiotonic Agents/pharmacology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Heart Rate/drug effects , Heart Ventricles/drug effects , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Male , Mice, Inbred C57BL , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Risk Factors , Tablets
6.
Chin J Integr Med ; 23(9): 643-647, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28861886

ABSTRACT

Ventricular remodeling (VR) can be induced by myocardial injury, leading to progressive cardiac dysfunction and heart failure, and is associated with high morbidity and mortality. Despite being studied for more than 3 decades, current therapeutic strategies still remain unsatisfactory in effificacy, expensive, and with side effects and drug resistances. Chinese medicine (CM) has been used to treat heart diseases for thousands of years. This article reviews the published studies on the mechanisms and therapeutic applications of CM in VR. The major aspects include: mechanistic studies of VR, molecular biology and myocardial functional studies of CM therapies on VR, and mechanism of CM therapies on VR.


Subject(s)
Drugs, Chinese Herbal/pharmacology , Precision Medicine , Ventricular Remodeling/drug effects , Humans , Signal Transduction/drug effects
7.
Sci Rep ; 7: 42843, 2017 02 16.
Article in English | MEDLINE | ID: mdl-28205629

ABSTRACT

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, GSK3ß 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 GSK3ß, 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/GSK3ß, and GATA4 signaling pathway.


Subject(s)
Drugs, Chinese Herbal/administration & dosage , GABA Plasma Membrane Transport Proteins/metabolism , Heart Failure/prevention & control , Myocytes, Cardiac/drug effects , Animals , Cell Nucleus/metabolism , Cell Survival/drug effects , Cells, Cultured , Constriction, Pathologic , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Echocardiography , Gene Expression Regulation/drug effects , Glycogen Synthase Kinase 3 beta/metabolism , Heart Failure/etiology , Heart Failure/metabolism , Heart Failure/physiopathology , Humans , MAP Kinase Signaling System/drug effects , Mice , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Rats
8.
Oncotarget ; 8(65): 108958-108969, 2017 Dec 12.
Article in English | MEDLINE | ID: mdl-29312582

ABSTRACT

Shexiang Tongxin dropping pill (STDP) is a formulae of Chinese Medicine commonly used to treating angina pectoris in China. However, its mechanism of action is still yet unclear. This study investigated the roles of STDP on myocardial ischemia injury. We constructed a rat model of myocardial injury (isoproterenol subcutaneous injection, i.h, 85 mg/kg/day for 2 days), and compared among 4 groups: CON (control), ISO (ischemic injury model), MET (metoprolol), and STDP. Serum contents of Troponin I (cTnI), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), alpha-hydroxybutyric dehydrogenase (α-HBD), and Aspartate Aminotransferase were detected and five STDP doses (1, 10, 100, 1000 and 10000 mg/kg/day) were chosen to obtain a dose-response curve. Western-blot was used to detect phosphorylations of extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT), and camodulin kinase II (CamkII). Furthermore, an ERK1/2 inhibitor PD98059, a phosphatidylinositol-3-kinase inhibitor, LY294002, and a CamKII inhibitor, KN-93 were administered i.h. RESULTS: cTnI, CK, CK-MB, α-HBD, and LDH were significantly lower in STDP than ISO (P<0.05). STDP exhibited a dose-dependent effect with a half maximal inhibitory concentration of 42 mg/kg/day. Phosphorylation of ERK1/2 was enhanced in the STDP group (vs. ISO, P<0.05), while AKT and CamkII were not changed. Further, the protective effects of STDP were offset by PD98059 administration i.h. In conclusion, STDP protected against the ISO-induced myocardial ischemic injury via an ERK1/2 signaling pathway, which provided a mechanism to support clinical applications of STDP as treatment for ischemic heart disease.

9.
Chin J Integr Med ; 23(1): 40-47, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27787719

ABSTRACT

OBJECTIVE: To analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury. METHODS: Myocardial 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. RESULTS: There 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). CONCLUSION: Salvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.


Subject(s)
MAP Kinase Signaling System , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocardial Reperfusion Injury/drug therapy , Plant Extracts/therapeutic use , Animals , Blotting, Western , Cardiotonic Agents/pharmacology , Cardiotonic Agents/therapeutic use , Flavonoids/pharmacology , Heart Ventricles/drug effects , Heart Ventricles/pathology , MAP Kinase Signaling System/drug effects , Male , Mice, Inbred C57BL , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/pathology , Organ Size/drug effects , Phosphorylation/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Protein Kinase Inhibitors/pharmacology , Staining and Labeling
10.
PLoS One ; 11(11): e0166560, 2016.
Article in English | MEDLINE | ID: mdl-27893819

ABSTRACT

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.


Subject(s)
Benzofurans/pharmacology , Heart Failure/pathology , Signal Transduction/drug effects , Animals , Aorta, Thoracic/surgery , Benzofurans/chemistry , Blood Pressure/drug effects , Cell Line , Disease Models, Animal , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , GATA4 Transcription Factor/metabolism , Heart Failure/metabolism , Heart Ventricles/diagnostic imaging , Male , Mice , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Natriuretic Peptide, Brain/blood , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Rats
11.
BMC Complement Altern Med ; 16(1): 447, 2016 Nov 08.
Article in English | MEDLINE | ID: mdl-27825334

ABSTRACT

BACKGROUND: Danlou tablets, a patented Chinese Medicine, have been long approved for the treatment of ischemic heart disease in China. While numerous empirical observations suggested Danlou tablets could decrease frequency and duration of angina pectoris attacks, evidence supporting its efficacy on cardiac remodeling remains inadequate. Therefore, this pilot trial was designed to determine whether Danlou tablets would reduce adverse left ventricular (LV) remodeling in patients with myocardial infarction (MI). METHODS AND RESULTS: Eligible patients with acute MI were enrolled and randomly assigned to Danlou tablets or placebo groups, superimposed on standard treatment for MI. Then, in addition to assessment of the clinical outcome, the changes in LV volumes were evaluated by a serial echocardiography. In total, 83 patients (Danlou tablets 42 and placebo 41) completed 90 days of treatment and had complete baseline and outcome data. Standard echocardiographic evaluations revealed significant differences in the change of LV end-diastolic volume index (LVEDVi) between group of patients treated with Danlou tablets and the placebo group (-4.49 ± 7.29 vs. -0.34 ± 9.01 mL/m2, P < 0.001). The reduction in LVEDVi was independent of beta-blocker, ACE inhibitors/ARBs use. Furthermore, treatment with Danlou tablets significantly reduced LV end-systolic volume index (-4.09 ± 5.85 vs. -0.54 ± 5.72 mL/m2, P < 0.001) and improved the LV ejection fraction (4.83 ± 9.23 vs. 0.23 ± 8.15 %, P < 0.001), as compared to placebo. Meaningfully, the incidence of the major adverse cardiovascular events was also lower in patients receiving Danlou tablets (P < 0.05). CONCLUSION: Superimposed on the standard pharmacologic treatment, Danlou tablets significantly reversed post-MI adverse LV remodeling, thereby contributed to the overall positive clinical outcome. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02675322 (February 1, 2016).


Subject(s)
Drugs, Chinese Herbal/administration & dosage , Myocardial Infarction/complications , Ventricular Dysfunction, Left/drug therapy , Adult , Aged , Aged, 80 and over , China , Double-Blind Method , Female , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Remodeling/drug effects , Young Adult
12.
Basic Res Cardiol ; 111(5): 57, 2016 09.
Article in English | MEDLINE | ID: mdl-27506532

ABSTRACT

Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4 (-/-) mice showed aberrant cardiac voltage-gated ion channel sialylation and gating that contribute to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology revealed modest dilated and thinner-walled left ventricles without increased fibrosis in ST3Gal4 (-/-) mice starting at 1 year of age. Cardiac calcineurin expression in younger (16-20 weeks old) ST3Gal4 (-/-) hearts was significantly reduced compared to WT. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the ST3Gal4 (-/-) heart, as suggested by previous reports describing the functional implications of reduced cardiac calcineurin levels. TAC'd ST3Gal4 (-/-) mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT hearts remained well-adapted throughout (ejection fraction, ST3Gal4 (-/-) = 34 ± 5.2 %; WT = 53.8 ± 7.4 %; p < 0.05). Thus, a novel, sialo-dependent model for DCM/HF is described in which clinically relevant reduced sialylation results in increased arrhythmogenicity and reduced cardiac calcineurin levels that precede cardiomyopathy and TAC-induced HF, suggesting a causal link among aberrant sialylation, chronic arrhythmia, reduced calcineurin levels, DCM in the absence of a pathologic stimulus, and stress-induced HF.


Subject(s)
Cardiomyopathy, Dilated/metabolism , Cardiomyopathy, Dilated/physiopathology , Heart Failure/metabolism , Heart Failure/physiopathology , Animals , Blotting, Western , Disease Models, Animal , Male , Mice , Mice, Knockout , Sialyltransferases/deficiency , beta-Galactoside alpha-2,3-Sialyltransferase
13.
Chin J Integr Med ; 21(9): 662-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26142341

ABSTRACT

BACKGROUND: It has been shown that administration of statins reduced the risk of peri-procedural myocardial damage. However, it remains unclear whether Chinese medicine Danlou Tablet (), similar to statins, may protect patients undergoing percutaneous coronary intervention (PCI) from peri-procedural myocardial damage. OBJECTIVE: To demonstrate the hypothesis whether treatment with Danlou Tablet would improve clinical outcome in patients undergoing selective PCI with non-ST elevation acute coronary syndrome (NSTE-ACS) in China. METHODS: Approximately 220 patients with unstable angina or non-ST-segment elevation myocardial infarction undergoing PCI will be enrolled and randomized to Danlou Tablet treatment (4.5 g/day for 2 days before intervention, with a further 4.5 g/day for 90 days thereafter) or placebo. All patients will not receive Danlou Tablet before procedure. The primary end point is to evaluate the incidence of cardiac death, myocardial infarction or unplanned re-hospitalization and revascularization after 30 days in patients undergoing selective PCI treated with Danlou Tablet compared with placebo. Secondary endpoints include the incidence of peri-procedural myocardial injury, 3-month clinical outcomes, the quality of life and Chinese medicine syndromes assessment. CONCLUSION: This study protocol will provide important evidence of Danlou Tablet treatment on the peri-procedural myocardial injury in patients with NSTE-ACS undergoing selective PCI, which may support a strategy of routine Danlou Tablet therapy to improve the clinical outcomes.


Subject(s)
Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/drug therapy , Drugs, Chinese Herbal/therapeutic use , Electrocardiography , Myocardium/pathology , Percutaneous Coronary Intervention , Endpoint Determination , Humans , Sample Size , Ultrasonography
14.
Article in English | MEDLINE | ID: mdl-25093027

ABSTRACT

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P < 0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT.

16.
Article in English | MEDLINE | ID: mdl-24073004

ABSTRACT

Myocardial ischemia/reperfusion (I/R) can induce lethal ventricular arrhythmia and myocardial infarction. One of the clinical strategies for managing patients with high risk of myocardial I/R is to prevent the occurrence of arrhythmias and limit the size of infarction following a coronary episode. Tongguan Capsule (TGC) is one of the popular herbal remedies in treating coronary artery disease in the clinics of Chinese medicine. However, the potential roles and mechanisms of TGC in reducing I/R injury are still unclear. The present study statistically assessed the effectiveness of TGC in reducing I/R injury by comparing the infarct size (IS), risk region (RR), and arrhythmia (in electrocardiogram) among four groups of surgically created mice models of myocardial I/R: SHAM, I/R, VER (I/R with verapamil 20 mg/kg pretreatment), and TGC (I/R with TGC 5 g/kg/d pretreatment). We found that IS was significantly smaller in the TGC and VER groups than I/R group, and the incidence of arrhythmias was reduced in the TGC group compared with I/R group, although there were no differences in RR among the four groups. We conclude that TGC is effective in reducing I/R injury in mice. These results provided an experimental basis for clinical application of TGC in reducing I/R injury.

17.
Article in English | MEDLINE | ID: mdl-23024695

ABSTRACT

Objective. To determine the impact of an integrative medicine clinical pathways (CPs) on the length of in-hospital stay and on outcomes for patients with acute myocardial infarction (AMI). Methods. A multicenter nonrandomized controlled trial enrolling 197 consecutive patients with AMI at eight urban TCM hospitals was conducted between 1 January 2010 and 31 October 2010. These patients were enrolled in the interventional group after the CPs had been implemented. The control group included 405 patients with AMI from eight hospitals; these patients were treated between 1 January 2008 and 31 December 2009, before the CPs were implemented. Outcome measures were the length of hospital stay costs of medical care, and major cardiovascular events (MACEs) during hospitalization. Results. Compared with the control group, the patients in intervention group had a shorter length of hospital stay (9.2 ± 4.2 days versus 12.7 ± 8.6 days, P < 0.05), and reduced healthcare costs in hospital (46365.7 ± 18266.9 versus 52866.0 ± 35404.4, P < 0.05). There were statistically significant differences in MACE between the two groups during the hospitalization period (2.5% versus 6.9%, P = 0.03). Conclusion. These data suggest that the development and implementation of the clinical pathways based in Integrative Medicine could further improve quality of care and outcome for patients with AMI.

19.
Clin Exp Pharmacol Physiol ; 37(3): 296-302, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19719751

ABSTRACT

1. Insulin-like growth factor (IGF)-I plays an important role in the pathogenesis of heart disease and has been shown to strongly induce the proliferation of cardiac fibroblasts (CFs). It remains unknown whether 14-3-3 proteins, which are associated the regulation of signal transduction, affect IGF-I-induced CF proliferation. 2. In the present study, we investigated the effects of 14-3-3 proteins on CF proliferation in response to IGF-I. Proliferation of CFs was determined by cell counting and a bromodeoxyuridine incorporation assay. Phosphorylation of signalling molecules was evaluated by western blottling. Activity of nuclear factor of activated T cells (NFAT) was examined using a dual luciferase reporter gene assay and immunofluorescence. 3. It was found that adenovirus-mediated transfection of YFP-R18 peptide (AdR18), a known inhibitor of 14-3-3, significantly enhanced IGF-I-induced CF proliferation. This potentiation arose from an increase in phosphorylation of phosphatidylinositol 3-kinase (PI3-K) and AKT (protein kinase B), inactivation of glycogen synthesis kinase (GSK) 3beta and increased NFAT activity. 4. Collectively, the results of the present study suggest that 14-3-3 proteins inhibit IGF-I-induced CF proliferation via a PI3-K-dependent NFAT signalling pathway. This finding may contribute to our understanding of the function of 14-3-3 proteins in the heart.


Subject(s)
14-3-3 Proteins/metabolism , Cell Proliferation , Fibroblasts/cytology , Insulin-Like Growth Factor I/pharmacology , Myocardium/cytology , Phosphatidylinositol 3-Kinase/physiology , 14-3-3 Proteins/antagonists & inhibitors , Animals , Cell Line , Cell Proliferation/drug effects , Cells, Cultured , Fibroblasts/enzymology , Fibroblasts/metabolism , Humans , Mice , Mice, Inbred C57BL , Myocardium/metabolism , Signal Transduction/drug effects , Signal Transduction/physiology
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