Mitochondria-associated endoplasmic reticulum membranes as a therapeutic target for cardiovascular diseases.

Cardiovascular diseases (CVDs) are currently the leading cause of death worldwide. In 2022, the CVDs contributed to 19.8 million deaths globally, accounting for one-third of all global deaths. With an aging population and changing lifestyles, CVDs pose a major threat to human health. Mitochondria-associated endoplasmic reticulum membranes (MAMs) are communication platforms between cellular organelles and regulate cellular physiological functions, including apoptosis, autophagy, and programmed necrosis. Further research has shown that MAMs play a critical role in the pathogenesis of CVDs, including myocardial ischemia and reperfusion injury, heart failure, pulmonary hypertension, and coronary atherosclerosis. This suggests that MAMs could be an important therapeutic target for managing CVDs. The goal of this study is to summarize the protein complex of MAMs, discuss its role in the pathological mechanisms of CVDs in terms of its functions such as Ca2+ transport, apoptotic signaling, and lipid metabolism, and suggest the possibility of MAMs as a potential therapeutic approach.

Gut-derived short-chain fatty acids bridge cardiac and systemic metabolism and immunity in heart failure.

Heart failure (HF) represents a group of complex clinical syndromes with high morbidity and mortality and has a significant global health burden. Inflammation and metabolic disorders are closely related to the development of HF, which are complex and depend on the severity and type of HF and common metabolic comorbidities such as obesity and diabetes. An increasing body of evidence indicates the importance of short-chain fatty acids (SCFAs) in regulating cardiac function. In addition, SCFAs represent a unique class of metabolites and play a distinct role in shaping systemic immunity and metabolism. In this review, we reveal the role of SCFAs as a link between metabolism and immunity, which regulate cardiac and systemic immune and metabolic systems by acting as energy substrates, inhibiting the expression of histone deacetylase (HDAC) regulated genes and activating G protein-coupled receptors (GPCRs) signaling. Ultimately cardiac efficiency is improved, cardiac inflammation alleviated and cardiac function in failing hearts enhanced. In conclusion, SCFAs represent a new therapeutic approach for HF.

The effectiveness and safety of Chinese Patent Medicines based on syndrome differentiation in patients following percutaneous coronary intervention due to acute coronary syndrome (CPM trial): A nationwide Cohort Study.

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.

Potential Mechanisms Between HF and COPD: New Insights From Bioinformatics.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are closely related in clinical practice. This study aimed to investigate the co-genetic characteristics and potential molecular mechanisms of HF and COPD. HF and COPD datasets were downloaded from gene expression omnibus database. After identifying common differentially expressed genes (DEGs), the functional analysis highlighted the critical role of extracellular matrix and ribosomal signaling pathways in both diseases. In addition, GeneMANIA's results suggested that the 2 diseases were related to immune infiltration, and CIBERSORT suggested the role of macrophages. We also discovered 4 TFs and 1408 miRNAs linked to both diseases, and salbutamol may positively affect them.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Heart failure with preserved ejection fraction and non-alcoholic fatty liver disease: new insights from bioinformatics.

AIMS: Heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) are related conditions with an increasing incidence. The mechanism of their relationship remains undefined. Here, we aimed to explore the potential mechanisms, diagnostic markers, and therapeutic options for HFpEF and NAFLD. METHODS AND RESULTS: HFpEF and NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were screened for functional annotation. A protein-protein interaction network was constructed based on the STRING database, and hub genes were analysed using GeneMANIA annotation. ImmuCellAI (Immune Cell Abundance Identifier) was employed for analysis of immune infiltration. We also used validation datasets to validate the expression levels of hub genes and the correlation of immune cells. To screen for diagnostic biomarkers, we employed the least absolute shrinkage and selection operator and support vector machine-recursive feature elimination. Drug signature database was used to predict potential therapeutic drugs. Our analyses identified a total of 33 DEGs. Inflammation and immune infiltration played important roles in the development of both diseases. The data showed a close relationship between chemokine signalling pathway, cytokine-cytokine receptor interaction, calcium signalling pathway, neuroactive ligand-receptor interaction, osteoclast differentiation, and cyclic guanosine monophosphate-protein kinase G signalling pathway. We demonstrated that PRF1 (perforin 1) and IL2RB (interleukin-2 receptor subunit beta) proteins were perturbed by the diseases and may be the hub genes. The analysis showed that miR-375 may be a potential diagnostic marker for both diseases. Our drug prediction analysis showed that bosentan, eldecalcitol, ramipril, and probucol could be potential therapeutic options for the diseases. CONCLUSIONS: Our findings revealed common pathogenesis, diagnostic markers, and therapeutic agents for HFpEF and NAFLD. There is need for further experimental studies to validate our findings.

Guanxinning Injection Combined With Ischemic Postconditioning Attenuate Myocardial Ischemic Reperfusion Injury in Chronic Renal Failure Rats by Modulating Mitochondrial Dynamics.

Purpose: Salvia miltiorrhiza Bge. (Danshen, DS) and Ligusticum chuanxiong Hort. (Chuanxiong, CX) have been widely used in traditional Chinese medicine to prevent and treat myocardial ischemia and renal insufficiency, and their extracts (Guanxinning injection, GXN) have been reported to exhibit antioxidant, anti-inflammatory, and anti-ischemia-reperfusion injury properties. It is well-established that ischemic postconditioning (IPOC) can protect against myocardial ischemia-reperfusion (I/R) injury in rats with chronic renal failure (CRF). However, little is known on whether GXN combined with IPOC may affect myocardial I/R injury in CRF rats. We sought to observe the effect of GXN combined with IPOC on myocardial I/R injury in CRF rats by quantifying changes in the expression of proteins related to mitochondrial dynamics. Materials and Methods: In a survey, 90 Wistar rats were randomly divided into 6 groups (15 rats per group): CRF group, I/R group, comorbid group (CRF + I/R), IPOC group, IPOC + GXN group and the sham group. Changes in blood myocardial injury markers, urea, and creatinine were analyzed. Heart tissues were harvested for histomorphometry and western blotting when rats were sacrificed. Myocardial infarction area was measured by Evans blue and Triphenyltetrazolium chloride solution staining. The expressions of mitochondrial fission relative proteins (DRP1 and FIS1) and mitochondrial fusion relative proteins (OPA1 and MFN1) were detected by western blotting. Results: IPOC could significantly decrease myocardial injury markers and myocardial area of necrosis (AN)/area at risk (AAR) of the comorbid model rats. Further results showed that GXN combined with IPOC could significantly reduce CK-MB levels and myocardial AN/AAR in comorbid model rats compared with the IPOC group. Meanwhile, both IPOC and IPOC + GXN significantly reduced DRP1 levels and increased the MFN1 and OPA1 protein levels in the comorbid model rats. However, compared with the IPOC group, MFN1 and OPA1 protein levels increased significantly in the IPOC + GXN group. Conclusion: Extracts of DS and CX combined with IPOC exert a protective effect against myocardial I/R injury in rats with CRF, mediated by increased expression of mitochondrial fusion proteins (MFN1 and OPA1).

Mechanisms and Efficacy of Traditional Chinese Medicine in Heart Failure.

Heart failure (HF) is one of the main public health problems at present. Although some breakthroughs have been made in the treatment of HF, the mortality rate remains very high. However, we should also pay attention to improving the quality of life of patients with HF. Traditional Chinese medicine (TCM) has a long history of being used to treat HF. To demonstrate the clinical effects and mechanisms of TCM, we searched published clinical trial studies and basic studies. The search results showed that adjuvant therapy with TCM might benefit patients with HF, and its mechanism may be related to microvascular circulation, myocardial energy metabolism, oxidative stress, and inflammation.

Panax quinquefolium saponin Optimizes Energy Homeostasis by Modulating AMPK-Activated Metabolic Pathways in Hypoxia-Reperfusion Induced Cardiomyocytes.

OBJECTIVE: To investigate the effects and underlying mechanisms of Panax quinquefolium saponin (PQS) on energy deficiency in hypoxia-reperfusion (H/R) induced cardiomyocytes. METHODS: The H/R injury involved hypoxia for 3 h and then reperfusion for 2 h. Cardiomyocytes recruited from neonatal rat ventricular myocytes (NRVMs) were randomly divided into control, H/R, H/R+compound C (C.C), H/R+PQS, and H/R+C. C+PQS groups. BrdU assay, lactase dehydrogenase (LDH) leakage and early apoptosis rate were evaluated to assess cell damages. Contents of high energy phosphate compounds were conducted to detect the energy production. Protein expression levels of adenosine monophosphate-activated protein kinase a (AMPKα), glucose transporter 4 (GLUT4), phosphate fructose kinase 2 (PFK2), fatty acid translocase/cluster of differentiation 36 (FAT/CD36), and acetyl CoA carboxylase 2 (ACC2) in the regulatory pathways were measured by Western blotting. Immunofluorescence staining of GLUT4 and FAT/CD36 was used to observe the mobilization of metabolic transporters. RESULTS: PQS (50 mg/L) pretreatment significantly alleviated H/R-induced inhibition of NRVMs viability, up-regulation of LDH leakage, acceleration of early apoptosis, and reduction of energy production (P<0.05). Compared with the H/R group, up-regulated expression of AMPKα, GLUT4, PFK2, FAT/CD36 and ACC2 were observed, and more GLUT4 and FAT/CD36 expressions were detected on the membrane in the H/R+PQS group (P<0.05). These effects of PQS on H/R-induced NRVMs were eliminated in the H/R+C.C+PQS group (P<0.05). CONCLUSION: PQS has prominent advantages in protecting NRVMs from H/R-induced cell damages and energy metabolic disorders, by activation of AMPKα-mediated GLUT4-PFK2 and FAT/CD36-ACC2 pathways.

A multi-center, randomized, double-blind, placebo-parallel controlled trial for the efficacy and safety of shenfuqiangxin pills in the treatment of chronic heart failure (Heart-Kidney yang deficiency syndrome).

BACKGROUND: Heart failure (HF) is the final stage of various cardiac diseases with poor prognosis. The integrated traditional Chinese medicine (TCM) and western medicine therapy has been considered as a prospective therapeutic strategy for chronic heart failure (CHF). There have been small clinical trials and experimental studies to demonstrate the efficacy of Shenfu Qiangxin Pills (SFQX) for treating CHF, however, there is still a lack of further high-quality trial. This paper describes the protocol for the clinical assessment of SFQX in CHF (heart-kidney Yang deficiency syndrome) patients. METHODS: A randomized, double-blind, parallel-group, placebo-controlled, multi-center trial will assess the efficacy and safety of SFQX in the treatment of CHF. 352 patients with CHF (heart-kidney Yang deficiency syndrome) from 22 hospitals in China will be enrolled. Besides their standardized western medicine, patients will be randomized to receive treatment of either SFQX or placebo for 12 weeks. The primary outcome is the plasma N-terminal pro-B-type natriuretic peptide levels, which will be measured uniformly by the central laboratory. The secondary outcomes include composite endpoint events (hospitalization due to worsening HF, all-cause mortality, other serious cardiovascular events), echocardiography indicators, grades of the New York Heart Association (NYHA) functional classification, the 6-minute walk test (6MWT) results, Minnesota Living With Heart Failure Questionnaire and TCM syndrome scores. DISCUSSION: The integrated TCM and western medicine therapy has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of SFQX in the treatment of CHF. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000028777 (registered on January 3, 2020).

The efficacy of Chinese herbal medicines on acute coronary syndrome with renal insufficiency after percutaneous coronary intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Chuanxiong capsule consists of Angelica sinensis radix and Chuanxiong rhizome, which are used in the traditional Chinese medicine for the treatment of coronary artery disease, and Xinyue capsule is composed of panax quinquefolius saponin extracted from leaves and stems of Panax quinquefolium L, which has the functions of anti-myocardial ischemia, improving myocardial energy metabolism and inhibiting apoptosis of cardiomyocytes. OBJECTIVE: To observe the role of Chinese herbal medicines in the cardiovascular outcome among patients with acute coronary syndrome (ACS) and renal insufficiency after percutaneous coronary intervention (PCI). METHODS: The subjects came from the 5C trial (chictr.org number: chictr-trc-07000021), post-PCI patients suffered from ACS with mild-to-moderate renal insufficiency (30 mL•min-1•1.73 m-2 < estimated glomerular filtration rate≤89 mL•min-1•1.73 m-2) included. The study population consisted of 215 subjects in the control group who were treated with western medicine standard therapy, and 211 subjects in the treatment group who were treated with Chinese herbal medicines (Fufang Chuanxiong Capsule and Xinyue Capsule) for 6 months on the basis of western medicine standard therapy. All were followed for 1 year. The primary endpoint included the composite of cardiac death, nonfatal recurrent myocardial infarction, and ischemia-driven revascularization. Secondary endpoint included the composite of stroke, congestive heart failure, and readmission for ACS. The serum creatinine and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After 1 year follow-up of two groups, there were 16 cases of primary endpoint in the control group and 6 cases of primary endpoint in the treatment group [absolute risk reduction (ARR): 0.046, 95%CI: 0.004-0.088; relative risk (RR): 0.38, 95%CI: 0.15-0.96, P = 0.040]. There were 15 cases of secondary endpoint in the control group and 5 cases of secondary endpoint in the treatment (ARR: 0.041, 95%CI: 0.006-0.086; RR: 0.34, 95%CI: 0.13-0.92, P = 0.033). The eGFR in the treatment group was significantly higher than that in the control group (75.19 ±â€¯16.74 mL min-1·1.73 m-2 VS 72.03 ±â€¯14.96 mL min-1·1.73 m-2, P < 0.05). The eGFR in the treatment group was significantly higher after the intervention with Chinese herbal medicines than that before intervention (72.27 ±â€¯11.83 mL min-1·1.73 m-2 VS 75.19 ±â€¯16.74 mL min-1·1.73 m-2, P < 0.05). CONCLUSION: Chinese herbal medicines plus western medicine standard therapy improved clinical outcomes in patients with ACS and mild-to-moderate renal insufficiency. Additionally, this study also demonstrated Chinese herbal medicines were useful in deferring decline of renal function.

Long-term follow-up of Chinese herbal medicines combined with conventional treatment in patients with acute coronary syndrome after percutaneous coronary intervention: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events. RESULTS: A total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group). CONCLUSION: CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

Resting heart rate associates with one-year risk of major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23-1.14; P = 0.100) for patients with RHR < 61 bpm, and 0.44 (95%CI: 0.23-0.85; P = 0.014) for those with RHR 61-76 bpm. For patients with RHR ≥ 61 bpm, an increase of 10 bpm in RHR was associated with an increase by 38.0% in the risk of MACE (AHR: 1.38; 95% CI: 1.04-1.83; P = 0.026). ACS patients after PCI with RHR >76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61-76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients.

[Efficacy of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus after Percutaneous Coronary Intervention: a Clinical Observation].

OBJECTIVE: To observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI). METHODS: In this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment. RESULTS: The incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01). CONCLUSION: Administration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI.

Traditional formula, modern application: chinese medicine formula sini tang improves early ventricular remodeling and cardiac function after myocardial infarction in rats.

SINI TANG (SNT) IS A TRADITIONAL CHINESE HERBAL FORMULA CONSISTING OF FOUR DIFFERENT HERBS: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor- ß 1 (TGF- ß 1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF- ß 1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI.

Anti-inflammatory effects of the chinese herbal formula sini tang in myocardial infarction rats.

The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor- α , interleukin-6, and interleukin-1 ß (TNF- α , IL-6, and IL-1 ß ) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF- α , IL-6, and IL-1 ß in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses.

Long-term effect of stent coating with zedoary essential components on neointimal formation in the porcine coronary artery.

OBJECTIVE: To examine the effect of the zedoary essential component-eluting stent (ZES) on a porcine coronary neointimal formation. METHODS: ZES, sirolimus-eluting stents (SES), and bare metal stents (BMS) were randomly implanted in three different major epicardial vessels in 36 balloon-injured pigs. Coronary angiography, optical coherence tomography, and histomorphological analysis were used to determine antihyperplasia effects. RESULTS: ZES and SES had a significantly larger lumen diameter and area, and reduced diameter and area of stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells in some arteries with SES compared with ZES (P<0.05). Injury scores were not different among the three groups at 30 and 90 days. The endothelialization score in the SES group was 2.69 ± 0.42 at 30 days and 2.83 ± 0.39 at 90 days compared with the ZES and BMS groups (both were 3.00 ± 0.00 at either 30 or 90 days, P<0.05). Well developed endothelium was observed in the ZES group, while incomplete endothelium and inflammatory cells were observed with stent struts partly naked at the vessel lumen in the SES group. CONCLUSION: The ZES inhibits neointimal hyperplasia with good endothelia coverage in the porcine balloon injury coronary model.

Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study.

Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n = 808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P = 0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P = 0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding.

[Effects of Salvia miltiorrhiza and Carthamus tinctorius aqueous extracts and compatibility on rat myocardial ischemic reperfusion injury].

OBJECTIVE: To separate and characterize aqueous extracts of Salvia miltiorrhiza and Carthamus tinctorius to efficient, high-throughput and strong polar components, to observe effects of their aqueous effective components compatibility on rat myocardial ischemic reperfusion injury. METHOD: Myocardial ischemic reperfusion injury model were established on SD rats by 40 min ligation of the left anterior descending artery and 120 min reperfusion. The rats were injected experimental drugs intravenously from femoral vein after 10 min ischemia. Rats were randomly divided into sham group (the suture around the left anterior descending coronary artery was not tied), model group, Danhong injection group (content of protocatechualdehyde is 0.05 g x L(-1), injection dosage equivalent to 1.80 g x kg(-1)), aqueous effective component of S. miltiorrhiza group (content of salvianolic acid B is 49 g x L(-1), injection dosage equivalent to 30.68 g x kg(-1)), aqueous effective component of S. miltiorrhiza group (content of hydroxysafflor yellow A is 31.76 g x L(-1), injection dosage equivalent to 17.87 g x kg(-1)), aqueous effective components compatibility of S. miltiorrhizae and C. tinctorius group (injection dosage is respectively 24.28 g x kg(-1) and 48.55 g x kg(-1)), each group have ten rats. Drugs were diluted with an equal dose of normal saline. The rats of sham group and model group were injected equivalent dosage of saline. The myocardial infarction size and the contents of serum cTnT and CK-MB were detected. The level of TXB2, 6-keto-PGF(1alpha) and platelet aggregation in blood plasma were investigated. RESULT: Compared with sham group, serum cTnT and CK-MB contents in model group increased significantly (P < 0.01). Compared with model group, myocardial infarction size and serum cTnT and CK-MB contents in aqueous effective component of S. miltiorrhiza group, aqueous effective component of C. tinctorius group and aqueous effective components compatibility of S. miltiorrhiza and C. tinctorius groups decreased significantly. Aqueous effective component of S. miltiorrhiza increased the level of 6-ke-to-PGF(1alpha), as well as decreased content of TXB2 and inhibited platelet aggregation (P < 0.01). Aqueous effective component of C. tinctorius also decreased the content TXB2 (P < 0.01). Improved extent of some detected markers in aqueous effective components compatibility of S. miltiorrhiza and C. tinctorius groups were better than that of Danhong injection group. CONCLUSION: Effective components compatibility of aqueous extracts from S. miltiorrhiza and C. tinctorius may reduce myocardial infarct size and leakage of myocardial enzyme, and increase the level of 6-keto-PGF1alpha, so as to inhibit platelet aggregation and prevent thrombosis, the result of which is to reduce myocardial ischemic reperfusion injury.

[Protective effect of fosinopril sodium pretreatment combined with ischemic postconditioning on rat heart underwent myocardial ischemia/reperfusion injury].

OBJECTIVE: To investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion. METHODS: Sixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA. RESULTS: Compared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01). CONCLUSION: Pretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.