Study of the mechanism of Shexiang Baoxin pill-mediated angiogenesis in acute myocardial infarction.

AIM: The Shexiang Baoxin pill (SBP) is a commonly used drug for the treatment of coronary artery disease in China. More recently, some studies have found that it improved coronary microvascular function. This study aimed to explore the possible mechanism by which the SBP promotes angiogenesis after acute myocardial infarction (AMI). METHODS: A rabbit model of acute myocardial infarction was established by ligating the left anterior descending coronary artery with silk thread, and the limb lead electrocardiogram was recorded to determine the success of the model. The rabbits were divided into a control group (SBP + normal rabbit group), a sham operation group, a saline + AMI group and an SBP + AMI group. There were 10 rabbits in each group. The animals were sacrificed and myocardial tissue was collected seven days after the operation. Haematoxylin-eosin staining was used to observe the histological changes in the rabbit myocardium in each group. The degree of acute myocardial infarction was observed with picric acid staining, which was used to detect the expression of vascular endothelial growth factor (VEGF), silent information regulator 1 (SIRT1), Beclin1 and mTOR protein in the myocardial tissue of each group. Immunofluorescence CD31-labelled microvascular density (MVD) was used to observe the vascular regeneration of the rabbits in each group. RESULTS: Compared with the normal saline + AMI group, the myocardial infarction area of the SBP + AMI group decreased and CD31 immunofluorescence-labelled MVD increased. Compared with the control and sham operation groups, the expression of VEGF, Beclin1 and mTOR in the normal saline + AMI group and the SBP + AMI group increased, while the expression of SIRT1 decreased. Compared with the normal saline + AMI group and the SBP + AMI group, the positive expression of VEGF, Beclin1, mTOR and SIRT1 in the SBP + AMI group was significantly increased. CONCLUSION: Autophagy was enhanced after acute myocardial infarction. SBP may affect angiogenesis through the SIRT1/mTOR signalling pathway after acute myocardial infarction to inhibit ventricular remodelling and a decline in cardiac function.

Association between miRNA-499 gene polymorphism and autoimmune diseases: A meta-analysis.

INTRODUCTION: The association between miRNA-499 rs3746444 and a variety of autoimmune diseases has been reported. However, these results were contradictory and just focused on one or two autoimmune diseases. The present study aims to examine the possible association between rs3746444 polymorphism and the risk of autoimmune diseases. METHODS: The studies that evaluated the association between miRNA-499 gene polymorphism and autoimmune diseases were retrieved. Five different genetic models were used to evaluate the association. The random-effects model was used to pool the effect sizes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the associations. Stratification analyses were performed by ethnicity and type of autoimmune diseases. False-positive report probability (FPRP) was performed for determining noteworthy associations. RESULTS: Seventeen articles (twenty studies) involving 4,376 cases and 4,991 controls were identified and included in our meta-analysis. The pooled ORs of all eligible case-control studies indicated a significant association between miRNA-499 gene polymorphism and autoimmune diseases: (T vs. C: OR = 0.877; 95% CI: 0.774, 0.993; P = 0.039). Stratified analysis indicated a significant association across both Caucasian (TT vs. TC+CC: OR = 0.779; 95% CI: 0.622, 0.976; P = 0.030) and Asian (T vs. C: OR = 0.895; 95% CI: 0.808, 0.992; P = 0.035) populations. There was also a significant association in Behcet's disease, rheumatoid arthritis, systemic lupus erythematosus, and ulcerative colitis populations. CONCLUSIONS: Our meta-analysis suggested that the miRNA-499 rs3746444 polymorphism was associated with an elevated risk of autoimmune diseases in the overall analysis as well as Caucasian and Asian populations.

A potential diagnostic pitfall in ST elevation: Acute pulmonary embolism or ST-segment elevation myocardial infarction.

The diagnosis of acute pulmonary embolism (APE) is a great challenge for physicians due to its nonspecific symptoms, and often missed or misdiagnosed as acute coronary syndrome. Electrocardiographic (ECG) abnormalities are seen in majority of patients with APE. Recently, APE with ST-segment elevation (STE) in leads V1 -V3 /V4 , mimicking ST-segment elevation myocardial infarction (STEMI), has been described. However, coronary angiography showed that the patient's coronary arteries were mostly normal. Herein, we describe a case of APE presenting with STE in V1 -V4 , along with severe stenosis of the left anterior descending (LAD) artery.

Atypical de Winter ECG pattern may be the mirror image of ST elevation.

BACKGROUND: The de Winter ECG pattern of ST-segment depression and tall symmetrical T waves, known as an ST elevation equivalent, accounts for approximately 2% of patients with occlusion of the proximal left anterior descending (LAD) coronary artery. The classic de Winter pattern is restricted to cases without ST elevation. However, mixed cases with different types of ST deviation have been described. Here, we describe an interesting case as an example of an ST elevation myocardial infarction (STEMI) equivalent, showing transient transmural ischemia of the inferolateral myocardium, with ECG changes that mimic the de Winter pattern.

The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials.

Background: Cardiovascular disease threatens the health and quality of life of individuals, particularly those with type II diabetes. Recently, some studies have reported the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the rates of hospitalization or urgent visits, resulting in IV therapy for heart failure in patients with type 2 diabetes mellitus (T2DM). Methods: We did a comprehensive search in electronic databases from inception through July 2020 for randomized-controlled trials, using the keywords "sodium-glucose cotransporter-2 inhibitor", "dapagliflozin", "heart failure", "cardiovascular outcomes", "major adverse cardiovascular events", "all-cause mortality", and "cardiovascular death". Random-effects summary odds ratios (OR) were constructed using M-L heterogeneity model. Results: Five trials with 5,252 patients were ultimately included. The incidence of hospitalization for heart failure (HHF) (n=4, OR=0.74; 95% CI, 0.61 to 0.88; I2 = 0%) and all-cause mortality (ACM, n=4, OR=0.76; 95% CI, 0.66 to 0.94; I2 = 0%); was reduced by dapagliflozin, respectively, in all heart failure patients, without obvious heterogeneity. The incidence of cardiovascular death in dapagliflozin was lower than that in placebo without statistically significant (CVD, n=5, OR=0.84; 95% CI, 0.69 to 1.03; I2 = 0%). In HFrEF subgroup, dapagliflozin was associated with a reduced incidence of hospitalization for heart failure (n=4, OR=0.74; 95% CI, 0.60 to 0.91; I2 = 0%), cardiovascular death (n=4, OR=0.72; 95% CI, 0.58 to 0.91; I2 = 8%), and all-cause mortality (n=3, OR=0.70; 95% CI, 0.50 to 0.99; I2 = 43%) without significant heterogeneity. In contrast, in the HFpEF subgroup, there was no difference in the incidence of cardiovascular death (n=2, OR=1.45; 95% CI, 0.95 to 2.22; I2 = 0%) and all-cause mortality (n=2, OR=1.04; 95% CI, 0.76 to 1.43; I2 = 0%) between dapagliflozin and placebo. Conclusion: In our study, dapagliflozin performed a statistical reduction in the rate of heart failure hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and diabetes. However, in the HFpEF subgroup, dapagliflozin did not show a significant cardiovascular protective effect.

Associations between erythropoietin polymorphisms and risk of diabetic microvascular complications.

We conducted a meta-analysis to evaluate the relationship between erythropoietin (EPO) polymorphisms and diabetic microvascular complications. We searched the PubMed, Embase, Cochrane library, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases for appropriate studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations. Ultimately, eight studies consisting of 2,861 cases and 2,136 controls were identified and included in our meta-analysis. Results with our genotype model indicated an association between rs1617640 polymorphisms and diabetic microvascular complications (TT vs. GG: OR = 1.544, 95% CI = 1.089-2.189, P = 0.015). No clear associations between the rs1617640 and rs507392 polymorphisms and diabetic retinopathy were observed. By contrast, rs551238 polymorphisms were associated with increased diabetic retinopathy risk (allele model: OR = 0.774, 95% CI = 0.658-0.911, P = 0.002; genotype model: AC vs. CC: OR = 0.598, 95% CI = 0.402-0.890, P = 0.011; dominant model: OR = 0.561, 95% CI = 0.385-0.817, P = 0.003; recessive model: OR = 0.791, 95% CI = 0.643-0.973, P = 0.026). These results indicate that EPO polymorphisms are a risk factor for diabetic microvascular complications.

Associations of MMP-2, BAX, and Bcl-2 mRNA and Protein Expressions with Development of Atrial Fibrillation.

BACKGROUND To examine changes of mRNA and protein expressions of MMP-2, Bcl-2, and BAX in atrial fibrillation (AF) patients, and investigate the correlations among these 3 biomarkers. MATERIAL AND METHODS Rheumatic heart disease patients (n=158) undergoing cardiac surgical procedures for mitral valve repair or replacement were included as the AF group (n=123), containing paroxysmal AF (n=42), persistent AF (n=36), and permanent AF (n=45). Rheumatic heart disease patients with sinus rhythm (SR) (n=35) were enrolled as the SR group (control group). Immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) were applied to detect the protein and mRNA expression levels of MMP-2, Bcl-2, and BAX. Apoptosis was observed with light and electron microscopes and detected by TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS Compared with the SR group, the left atrial diameters (LADs), protein and mRNA expression levels of MMP-2 and BAX, apoptotic index (AI), and Bcl-2/BAX ratio were evidently increased in the 3 AF groups, but protein and mRNA expression levels of Bcl-2 decreased in the AF groups (all P<0.05). Correlation analysis found that MMP-2 protein expression levels was positively correlated with BAX expression, but negatively correlated with Bcl-2 expression levels. CONCLUSIONS Our study results suggest that elevated MMP-2 expression and disturbance balance of Bcl-2/BAX expressions may be associated with the development and maintenance of AF. MMP-2 may be involved in the development of AF through promoting BAX expressions and inhibiting Bcl-2.

Plaque image characteristics, hyperhomocysteinemia, and gene polymorphism of homocysteine metabolism-related enzyme (MTHFR C677T) in acute coronary syndrome.

This study aims to investigate the correlation between the different characteristics of plaques, plasma level of homocysteine (Hcy), and gene polymorphism of Hcy metabolism-related enzyme. In this consecutive case-control study, we measured the plasma Hcy level using fluorescence biochemistry method and examined the gene polymorphism of Hcy metabolism-related enzyme methylenetetrahydrofolate reductase (MTHFR) C677T using TaqMan probe technology. We also examined these using intravascular ultrasound. We studied the characteristics of the plaque, measured the cross-sectional areas of the external elastic membrane and the lumen, calculated the plaque area, plaque burden, and eccentricity index, and examined the remodeling index. Hard plaques were more dominant in the (SPA) group, whereas soft plaques were more dominant in the acute coronary syndrome (ACS) group (P < 0.001). The risk of plaque rupture and thrombus is higher in the ACS group (P < 0.05). Compared with SPA group, plaque burden was heavier in the ACS group (P < 0.05), but the eccentricity index is significantly higher in SPA group than in the ACS group (P < 0.001). Positive remodeling was more frequent in ACS group, whereas negative remodeling was more frequent in the SPA group (P < 0.001). Plasma Hcy levels were higher in the unstable than in the stable plaque group (P < 0.001). The constituent ratio of MTHFR C677T genotype were different in stable plaque group and vulnerable plaque group (P < 0.05). The T genotype can increase the incidence rate of vulnerable plaque. Hcy and MTHFR C677T gene polymorphism were found to be risk factors for vulnerable plaque. Therefore, these can be used as indices to predict the instability of atherosclerotic plaque.