Different Anti-inflammatory Drugs on High-Sensitivity C-Reactive Protein in Patients After Percutaneous Coronary Intervention: A Pilot Randomized Clinical Trial.

ABSTRACT: Colchicine reduces atherothrombotic cardiovascular events in coronary artery disease because of its anti-inflammatory effect. However, the effects of the other anti-inflammatory drugs in coronary artery disease remain unclear. This study included 132 patients aged 18-80 years who completed the planned percutaneous coronary interventions and were treated with aggressive secondary prevention strategies for 4 weeks. The subjects were randomly assigned to 1 of the following treatment groups for 4 weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in high-sensitivity C-reactive protein (hsCRP) levels at the end of 4 weeks. In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male, and 28 (25.69%) were female. The percentage changes in hsCRP after 4 weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups, respectively. Compared with the control group, only the colchicine group showed significantly greater reduction in hsCRP levels ( P = 0.022). In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin, myeloperoxidase, and myeloblastin), platelet aggregation (glycoprotein VI), and endothelial damage (galectin-3) were reduced with colchicine therapy. These results show that of 3 anti-inflammatory drugs only colchicine could reduce hsCRP in patients after percutaneous coronary interventions.

Paeonol alleviates placental inflammation and apoptosis in preeclampsia by inhibiting the JAK2/STAT3 signaling pathway.

Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti-apoptosis and anti-inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl-phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme-linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF-α, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bax, Bcl-2, and caspase-3) were tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules. Here, Pae repressed the inflammatory response in the placenta of PE-like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF-α, IL-6, and IFN-γ and the increased concentrations and mRNA levels of IL-4. Apoptosis in the placentas of PE-like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved-caspase-3 and the upregulated Bcl-2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC-39100) reversed Pae treatment-mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

Plasma Level of Elabela in Patients with Coronary Heart Disease and Its Correlation with the Disease Classification.

This study aimed to evaluate the concentration of plasma elabela (ELA) in patients with coronary heart disease (CHD) and its correlation with the disease classification.We enrolled 238 patients diagnosed by coronary angiography as CHD and 86 controls. The CHD group was divided into three subgroups: stable angina (SA), unstable angina (UAP), and acute myocardial infarction (AMI). The plasma levels of ELA were measured in all participants and compared among different groups. The relationship between ELA and CHD classification was analyzed.ELA levels were markedly higher by 10.71% in patients with CHD than in controls (P < 0.05). The concentration of ELA in UAP and AMI subgroups were higher than in controls and SA subgroup. The former difference was significant (P < 0.05), but the latter was not. In addition, the ELA concentration was not correlated with SYNTAX score, left ventricular ejection fraction, and other biochemical variables.The newfound hormone, ELA, significantly increased in patients with UAP and AMI. There is a tendency that ELA levels might be correlated with CHD classification, but not with lesion severity. ELA may play a role in acute coronary syndrome.

Association Between Low-Dose Aspirin and Uric Acid in the Elderly: An Observational Retrospective Cross-Sectional Study.

PURPOSE: Uric acid is an independent factor for arteriosclerotic cardiovascular disease (ASCVD). Although aspirin is one of the most widely used agent in patients with ASCVD, there were only a few studies focusing on the effects of low-dose aspirin on uric acid metabolism with controversial results. The present study aimed to investigate an association between low-dose aspirin treatment for more than one month and serum uric acid (SUA) with its urinary excretion in elderly patients. PATIENTS AND METHODS: This paper presents an observational retrospective cross-sectional study to determine the association between continuous daily taking low-dose aspirin (50-100mg) for more than one month and SUA with fraction excretion of uric acid (FEUA) in elderly patients. A total of 506 inpatients equal or over 60 in Department of Geriatrics of Peking University First Hospital were enrolled from 2017 to 2020. About 41.9% of them were taking aspirin for more than one month, while others were not taking this medicine. The correlation between aspirin use and SUA or FEUA was analyzed, and group-comparison was performed in different dosage groups of aspirin. RESULTS: After correcting confounding factors, there is no remarkable correlation between taking low-dose aspirin and SUA or FEUA, but a decreasing trend (coefficients=-4.946) of SUA in hyperuricemia patients with low-dose aspirin was observed despite no obvious difference (P=0.534). Whether SUA or FEUA has no significant difference between 50mg/d and 100mg/d aspirin subjects. CONCLUSION: SUA and urinary uric acid excretion are not associated with using of 50-100mg/d aspirin for more than one month in elderly patients with ASCVD or at risk.

Identification of Potential Inhibitors Against the TGF-ß/BMPs-Activin Receptor- like Kinase 1 Signal Pathway.

INTRODUCTION: In many diseased states, especially fibrosis and cancer, TGF-ß family members are overexpressed and the outcome of signaling is diverted toward disease progression. As the result of activin receptor-like kinase 1 (ALK1) plays a key role in TGF-ß signaling, discovering inhibitors of ALK1 to block TGF-ß signaling for a therapeutic benefit has become an effective strategy. METHODS: In this work, ZINC15894217 and ZINC12404282 were identified as potential ALK1 inhibitors using molecular docking, molecular dynamics simulation and MM/PBSA calculations studies. The analysis of energy decomposition found that Val208, Val216, Lys229, Gly283, Arg334 and Leu337 acted as crucial residues for ligand binding and system stabilizing. RESULTS: In addition, these compounds displayed excellent pharmacological and structural properties, which can be further evaluated through in vitro and in vivo experiments for the inhibition of ALK1 to be developed as drugs against fibrosis and tumor. CONCLUSION: Overall, our study illustrated a time- and cost-effective computer aided drug design procedure to identify potential ALK1 inhibitors. It would provide useful information for further development of ALK1 inhibitors to improve disease related to TGF-ß signal pathway.

Ginsenoside Re enhances the survival of H9c2 cardiac muscle cells through regulation of autophagy.

We examined the effect of ginsenoside Re (G-Re) on autophagy in H9c2 cardiomyocytes cultured in glucose deprivation (GD). Levels of the membrane-bound autophagy-related microtubule-associated protein 1A/1B-light chain 3 (LC3) B-2 were measured via immunoblotting and immunofluorescence was conducted to assess autophagosome formation. GD H9c2 cells were treated with 100 µmol/l G-Re. Cell viability was determined in culture medium. Phosphorylated 5' AMP-activated protein kinase (AMPK)-α and mammalian target of rapamycin (mTOR) levels were measured to explore the mechanisms underlying the effects of G-Re on autophagy in GD cells. G-Re treatment inhibited autophagosome formation and may be beneficial to GD cardiomyocytes.

miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression.

Aspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes-PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B-and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B2 (TXB2) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3'-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.

Usage patterns and comfort of gardens: a seasonal survey of internal garden microclimate in the aged care homes of Chengdu City.

An increasing number of Chinese elders trade family care for institutional elder care, which poses an acute challenge due to the enormous number of elders. The internal garden of care homes is often the only green space supplied for the elderly. To elucidate the microclimate status of these internal gardens, three microclimate parameters (air temperature (Ta), relative humidity (RH), and solar radiation (SR) were measured in the gardens of eight care homes for the aged in Chengdu City (for 2015 and 2016). The results confirmed that all gardens showed effects of seasonal cooling (from 1.0 ± 0.7 to 2.00 ± 0.8 °C), humidification (from 2.8 ± 1.4 to 4.9 ± 2.0%), and weakening of solar radiation (from 52.3 ± 36.3 to 254.4 ± 124.1 w/m2). Even small internal gardens (130-4000 m2) could yield cooling effects in four seasons. Among garden subareas, the weakest SR, the lowest Ta, and the highest RH were all found in the rest area. Correlation analysis demonstrated that only in summer, the green coverage ratio of the garden significantly affected the microclimate. The observation showed that an average of 29.98% of the elderly used these internal gardens per day. The period of 8:00 am to 10:00 am was the elderly's favorite time to use the gardens. More than 68% of elders preferred to sit in the rest area. Thermal/humidity/radiation sensation votes indicated that the garden microclimate partially deviated from elders' comfortable levels, particularly in winter. The rest area showed the worst comfort level for the elders. A warmer, more humid, and more sun-exposed garden should be supplied to the elderly. Several greening strategies are proposed to improve the garden microclimate for the well-being of the elderly in the care homes.

Factors Influencing Aspirin Hyporesponsiveness in Elderly Chinese Patients.

BACKGROUND Aspirin hyporesponsiveness increases the risk of ischemic events. Therefore, it is important to investigate the factors influencing aspirin hyporesponsiveness. MATERIAL AND METHODS Patients aged 60 years or older who did not take aspirin before enrollment were included, with aspirin 100 mg/day administered after enrollment. The arachidonic acid-induced platelet aggregation rate (Ara) was measured by light transmission assay to evaluate aspirin responsiveness. Patients with Ara in the upper quartile after taking aspirin were assigned to the aspirin hyporesponsive group (Ara-Q4). RESULTS A total of 292 elderly patients were included. The median value of Ara after taking aspirin was 5.87% (interquartile range 3.86-10.04%). Compared with the aspirin non-hyporesponsive group (Ara-Q1-3, Ara ≤10.04%, n=220), the level of uric acid (UA) (341.30 µmol/L vs. 299.10 µmol/L, p=0.027) and the ratios of ß-blockers (9.72% vs. 2.27%, p=0.015) and diuretics (6.94% vs. 1.36%, p=0.036) were higher in the aspirin hyporesponsive group (Ara-Q4, Ara >10.04%, n=72). After multivariate adjustment, the results demonstrated baseline Ara (odds ratio [OR]: 1.030, 95% confidence interval [CI]: 1.004-1.056, p=0.021), UA level (OR: 1.003, 95% CI: 1.000-1.006, p=0.038), and ß-blockers use (OR: 5.487, 95% CI: 1.515-19.870, p=0.010) were independently and positively associated with aspirin hyporesponsiveness. CONCLUSIONS This study found that baseline Ara, UA level, and ß-blockers use were independently and positively associated with aspirin hyporesponsiveness in elderly Chinese patients, which needs to be validated in large-scale studies.

Association of Circulating Neuregulin-4 with Presence and Severity of Coronary Artery Disease.

Neuregulin-4 (Nrg4) is a newly discovered adipokine that is synthesized in many tissues and plays an important role in modulating systemic energy metabolism and in the development of metabolic disorders. However, little is known about the relationship between Nrg4 and coronary artery disease (CAD). In this study, we investigated the association between Nrg4 and the presence and severity of CAD.We enrolled 73 patients diagnosed by coronary angiography (CAG) as having CAD and 32 controls. The CAD group was divided into two subgroups according to their SYNTAX score. Plasma levels of Nrg4 were measured in all participants and compared among different groups. The relationship between Nrg4 and CAD was analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the usefulness Nrg4 in assessing the presence and severity of CAD.Nrg4 levels were negatively associated with the SYNTAX score (r = -0.401, P = 0.000). The patients with a higher SYNTAX score had significantly lower Nrg4 levels as compared with the low SYNTAX score subgroup and the controls (P < 0.05). The Nrg4 levels of the low SYNTAX score subgroup were much lower than controls (P < 0.05). Furthermore, an association between Nrg4 and CAD (odds ratio, 0.279; 95% confidence interval, 0.088-0.882) was observed. Nrg4 had 43.8% sensitivity and 96.9% specificity for identifying CAD, and 73.1% sensitivity and 87.3% specificity for identifying patients who had severe coronary artery lesions.Nrg4 levels were found to be inversely associated with the presence and severity of CAD.

CCR7/p-ERK1/2/VEGF signaling promotes retinal neovascularization in a mouse model of oxygen-induced retinopathy.

AIM: To investigate the role of CCR7/p-ERK1/2/VEGF signaling in the mouse model of oxygen-induced retinopathy (OIR). METHODS: Neonatal C57BL/6J mice were evenly randomized into four groups: normoxia, OIR, OIR control (treated with scramble siRNA), and OIR treated (treated with CCR7 siRNA). Normoxia group was not specially handled. Postnatal day 7 (P7) mice in the OIR group were exposed to 75%±5% oxygen for 5d (P7-P12) and then maintained under normoxic conditions for 5d (P12-P17). Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d (P12-P17). Retina samples were collected from all mice on P17, stained with adenosine diphosphatase (ADPase), and retinal neovascularization (RNV) was assessed. Retinas were also stained with hematoxylin and eosin (H&E) for RNV quantitation. The distribution and expression of CCR7, p-ERK1/2 and vascular endothelial growth factor (VEGF) were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: High oxygen promoted retinal neovascularization (P<0.05) and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process (P<0.05). CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERK1/2, and VEGF expression in the OIR mouse model (all P<0.05). CCR7 significantly enhanced the neovascularization and non-perfusion areas in the OIR group (P<0.05). CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls (P<0.05). CONCLUSION: These results suggest that CCR7/p-ERK 1/2/VEGF signaling plays an important role in OIR. CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.

[Association between CMTM5 gene rs723840 single nucleotide polymorphism and high on asprin platelet reactivity].

OBJECTIVE: To elucidate the correlation between the single nucleotide polymorphism of CKLF-like MARVEL transmembrane member 5 (CMTM5) gene rs723840 and the occurrence of high on aspirin platelet reactivity (HAPR). METHODS: The present study is a case-control study. A total of 210 hospitalized patients in Peking University First Hospital were enrolled. Aspirin response was assessed by 0.5 g/L arachidonic acid (AA)-induced platelet aggregation ratio (PR), and ≥ 3/4 quartile of PR of the population was defined as HAPR. Accordingly all the enrolled 210 coronary artery diseases (CAD) patients were divided into HAPR group and No-HAPR group. The genotypes were determined by polymerase chain reaction (PCR) and sequencing analysis for rs723840 of CMTM5 gene. RESULTS: The genotype frequencies in rs723840 C>T of CMTM5 gene conformed well to the Hardy-Weinberg equilibrium in both HAPR group and No-HAPR group. Between the two groups, the genotypes frequencies in HAPR and No-HAPR groups were 48.4%, 51.6%, 0.0% and 73.7%, 22.9%, 0.034%, respectively (P=0.004). The C, T allele frequencies were significantly different in the two groups (P=0.031,OR=0.501, 95% CI: 0.264-0.947). CONCLUSION: Our study finds a significant correlation between CMTM5 gene rs723840 polymorphism and high on aspirin platelet reactivity.

[Correlation between the level of the urinary 11-dehydrothromboxane B2 and the clinical efficacy of aspirin in patients with type 2 diabetes and coronary artery disease].

OBJECTIVE: To elucidate the correlation between urinary 11-dehydro-thromboxane B2 (11dhTxB2) and clinical efficacy of aspirin treatment in patients with type 2 diabete and coronary artery disease (CAD). METHODS: In this prospective cohort study, 169 aged patients with type 2 diabete accompanying CAD in Peking University First Hospital were enrolled. The level of urinary 11dhTxB2 was detected using enzyme-linked immuno-sorbent assay. Low aspirin response or high on aspirin platelet reactivity (HAPR) was defined as urinary 11dhTxB2>1 500 ng/g. All the included patients were divided into two groups based on the results, HAPR group and No-HAPR group. RESULTS: Baseline urinary 11dhTxB2 of the patients with type 2 diabete accompanying CAD was (3 687±3 052) ng/g, while the urinary 11dhTxB2 was (1 954±859) ng/g in patients after 100 mg/d aspirin treatment (P<0.001). Prevalence of HAPR in patients with type 2 diabete accompanying CAD were 32.5%. Within a mean follow-up time of 12 months, the outcomes occurred more frequently in HAPR group than in No-HAPR group (P<0.05). CONCLUSION: Urinary 11dhTxB2 can be recognized as an effective indicator in evaluating aspirin clinical efficacy of patients with type 2 diabete accompanying CAD.

Effective components of Panax quinquefolius and Corydalis tuber protect the myocardium by inhibiting platelet activation and improving the hypercoagulable state.

The aim of the present study was to investigate the effects of extract of Panax quinquefolius and Corydalis tuber (EPC) on platelet activation and the hypercoagulable state in rats with acute myocardial infarction (AMI). The MI model in Wistar rats was induced by coronary artery ligation. Sham surgery was performed as a control. The surviving rats that underwent MI surgery were divided into control (administered normal saline), metoprolol (9 mg/kg) and low-, moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively). Saline, metoprolol and EPC were administered by gastrogavage for two consecutive weeks. The morphological changes of the myocardium were assessed by hematoxylin and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF), D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the pathological changes of the myocardium. High-dose EPC decreased the serum concentration of vWF when compared with control group. Moderate and high doses of EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually decreased with EPC dose escalation. The results therefore demonstrated that EPC protects the myocardium by inhibiting platelet activation and improving the hypercoagulable state in a rat model of AMI.

[The clinical features of gastrointestinal bleeding complicating aortic stenosis].

OBJECTIVE: To deepen the understanding about Heyde's syndrome by investigating the clinical characteristics and prognosis of the patients with aortic valve stenosis complicating with gastrointestinal bleeding. METHODS: Patients with aortic valve stenosis and gastrointestinal bleeding coincidently admitted to our hospital from 2001 to 2011 were retrieved and analyzed. RESULTS: In all the 443 157 in-patients, 474 patients were diagnosed with aortic valve stenosis (0.11%, 474/443 157) and 14 patients (9 males and 5 females, aged 53-87 years old) with gastrointestinal bleeding coincidently(2.95%, 14/474). Among the 14 patients, 3 were moderate aortic valve stenosis, 11 severe aortic valve stenosis. The aortic valve peak flow velocity was 324-709 (480.54 ± 188.25) cm/s and the mean aortic valve pressure gradient was 21.04-91.56 (56.93 ± 29.90) mm Hg(1 mm Hg = 0.133 kPa).Heavy gastrointestinal bleeding was manifested in all the 14 patients with 1 of haematemesis and 13 of hematochezia.Hemoglobin (Hb) and red blood cell (RBC) count were significantly lower than the normal range [(69 ± 28) g/L and (2.71 ± 2.04)×10(12)/L, P < 0.05]. Their mean corpuscular volume(MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet(PLT) count, prothrombin time (PT) and international normalized ratio (INR) were in normal range [(90.21 ± 2.94) fl, (29.39 ± 1.99) pg, (327.57 ± 14.82) g/L, (185.13 ± 22.55)×10(9)/L, (11.4 ± 1.04) s and 1.22 ± 0.44, respectively]. Among all the 14 patients, 13 were over 65 years old and they all accepted gastrointestinal imaging (13/14).Vascular malformation of intestine was found in 6 patients with 4 lesions located in descending colon and 2 located in sigmoid colon.Hemorrhage foci were found in 2 patients with one of colon cancer, and another of duodenal ulcer, while no definite hemorrhage foci were found in the other 11 patients. A total of 6 patients with severe aortic valve stenosis underwent aortic valve replacement (AVR) successfully (6/11) and no recurrent gastrointestinal bleeding was ever found. Conservative treatment was performed in the other 5 patients with severe aortic valve stenosis (5/11) and resulted in sudden death in 2 patients (2/5). CONCLUSIONS: Prompt echocardiography and gastrointestinal endoscopy should be performed in the elderly patients with obscure gastrointestinal bleeding to facilitate the early diagnosis and treatment of Heyde's syndrome. AVR is a fundamental procedure to improve the prognosis of Heyde's syndrome.

Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and oxidative stress in a porcine model of acute myocardial infarction.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of American Ginseng and Corydalis Tuber has been widely used for treatment of cardiovascular diseases due to their anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate the anti-apoptotic effect of Shenyuan, which is composed of the bioactive components extracted from the mixture of American Ginseng and Corydalis Tuber, and to explore potential mechanisms involved in the regulation of apoptosis. MATERIALS AND METHODS: A porcine model of acute myocardial infarction (AMI) was established by ligation of the left anterior descending coronary artery. Thirty-eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg·d, n=6); Group M, AMI+moderate-dose Shenyuan (320 mg/kg·d, n=6); Group H, AMI+high-dose Shenyuan (400 mg/kg·d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg·d, n=6). The treatment of Shenyuan or Metoprolol started one week before AMI and continued for another two weeks after AMI. RESULTS: Treatment with all doses of Shenyuan as well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05), which was confirmed by TUNEL staining method. This anti-apoptotic effect was accompanied by less release of cardiac enzymes and limit of infarct size. In Group H, levels of MDA, 8-iso-prostaglandin F2α, GRP78/bip, calregulin, CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly increased (P < 0.05). In groups M and L, some results did not show statistical difference. There was no statistical difference in cardiac function between treatment groups and Group C. CONCLUSION: Shenyuan treatment significantly inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs with a large anterior wall AMI. This was accompanied by less release of cardiac enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may have a therapeutic role in improving the natural process of AMI.

Xuezhikang, extract of red yeast rice, improved abnormal hemorheology, suppressed caveolin-1 and increased eNOS expression in atherosclerotic rats.

BACKGROUND: Xuezhikang is the extract of red yeast rice, which has been widely used for the management of atherosclerotic disease, but the molecular basis of its antiatherosclerotic effects has not yet been fully identified. Here we investigated the changes of eNOS in vascular endothelia and RBCs, eNOS regulatory factor Caveolin-1 in endothelia, and hemorheological parameters in atherosclerotic rats to explore the protective effects of Xuezhikang. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats were divided into 4 groups (n = 12/group) group C, controls; group M, high-cholesterol diet (HCD) induced atherosclerotic models; group X, HCD+Xuezhikang; and group L, HCD +Lovastatin. In group X, Xuezhikang inhibited oxidative stress, down-regulated caveolin-1 in aorta wall (P<0.05), up-regulated eNOS expression in vascular endothelia and erythrocytes (P<0.05), increased NOx (nitrite and nitrate) in plasma and cGMP in erythrocyte plasma and aorta wall (P<0.05), increased erythrocyte deformation index (EDI), and decreased whole blood viscosity and plasma viscosity (P<0.05), with the improvement of arterial pathology. CONCLUSIONS/SIGNIFICANCE: Xuezhikang up-regulated eNOS expression in vascular endothelia and RBCs, increased plasma NOx and improved abnormal hemorheology in high cholesterol diet induced atherosclerotic rats. The elevated eNOS/NO and improved hemorheology may be beneficial to atherosclerotic disease.

[Value of 3-dimensional speckle tracking imaging to quantify regional left ventricular function in patients with coronary artery disease].

OBJECTIVE: To assess left ventricular (LV) strain by 3-dimensional speckle tracking imaging (3D-STI) in patients with coronary heart disease (CHD). METHODS: All subjects underwent invasive coronary angiography.2-dimensional and 3-dimensional echocardiography were performed in 52 subjects with suspected CHD. Longitudinal strain (LS) , circumferential strain (CS) , radial strain (RS) and area strain (AS) in 17 LV segments were acquired by 3D-STI respectively. RESULTS: According to coronary angiography results, 35 (76.1%)subjects were diagnosed as CHD, and 138 coronary branches were divided into the control group(25 branches, 18.1%), the mild stenosis group (31 branches, 22.5%), the moderate stenosis group (43 branches, 31.2%) and the severe stenosis group (39 branches, 28.2%).3D-STI was performed with reliable tracking quality in 46(88.5%) out of the 52 subjects initially enrolled in this study. 3D-STI showed:(1)LS was similar between mild stenosis group and the control group (P > 0.05) and significantly reduced in the moderate stenosis group compared with the control group(P < 0.05), and LS in some segments (MAS, AA, A, BAL, MAL, AL, BIS, MIS and AI) of moderate stenosis group were significantly decreased compared with the mild stenosis group (P < 0.05). LS of all segments in the severe stenosis group decreased significantly compared with the control group, the mild stenosis group and the moderate stenosis (P < 0.05). (2)RS was similar between mild stenosis group and the control group (P > 0.05) . RS in some segments (BAS,MA and BI) was significantly decreased in the moderate stenosis group compared with the control group(P < 0.05). RS was significantly decreased in the severe stenosis group compared with the control group and the mild stenosis group (except for AS,AL,MIS,MI and AI) (P < 0.05). (3) CS was similar between mild stenosis group and the control group (P > 0.05) and was significantly reduced in some segments (BAS,AS,BIL and BI) of the moderate stenosis group compared with the control group(P < 0.05). CS was significantly decreased in the severe stenosis group compared with the control group, the mild stenosis group and the moderate stenosis(P < 0.05). (4) AS was significantly decreased in the mild stenosis group compared with the control group(P < 0.05, except for BIL,MAL and BIS) and in all segments of the moderate stenosis group compared with the control group and the mild stenosis group(P < 0.05). AS was significantly decreased in the severe stenosis group compared with the control group, the mild stenosis group and the moderate stenosis(P < 0.05). The progressive decrease in AS was observed from the control group to the mild stenosis group, the moderate stenosis group and the severe stenosis group (P < 0.05). In addition, AS was negatively correlated with coronary artery Gensini score (r = -0.71, P < 0.01) . CONCLUSION: LV strain can be reliably quantified by 3D-STI. AS is a more sensitive parameter to detect coronary artery disease at early phase.