Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction.

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 ß, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION: LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Prognostic Significance of Triglyceride-Glucose Index for Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Insulin resistance (IR) represents a critical regulator in the development and progress of coronary artery disease (CAD). Triglyceride-glucose (TyG) index, a novel surrogate biomarker of IR, has been implicated in several cardiovascular diseases. Accordingly, we conduct a meta-analysis to elucidate the relationship between TyG index and adverse cardiovascular events in patients with CAD. Methods: To identify the studies examining the predictive capacity of the TyG index for adverse cardiovascular events in the setting of CAD, we performed a comprehensive literature retrieval of Scopus, PubMed, EMBASE, and Web of Science, from the inception of databases to October 5, 2021. We pooled the adjusted hazard ratio (HR) along with 95% CI using a random-effects model. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including all-cause death, cardiovascular death (CV death), myocardial infarction (MI), stroke, hospitalization for unstable angina or heart failure, and revascularization. The secondary outcomes were all-cause death, CV death, MI, stroke, and revascularization. Additionally, we conducted subgroup analyses stratified by diabetes status, age, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), category of TyG index, sample size, follow-up duration, and study design. Results: About 12 studies involving 28,795 patients with CAD were finally taken into the quantitative analysis. Our findings showed that there was a 2.14-fold higher risk of MACEs among CAD populations in the highest TyG group compared with those in the lowest TyG group (HR: 2.14, 95% CI: 1.69-2.71, P < 0.001). A greater risk of MACEs was observed in participants with higher BMI than those with lower BMI (P = 0.03 for interaction). In the analysis of secondary outcomes, we also observed a markedly increased risk of MI, stroke, and revascularization in the highest TyG group compared with the lowest TyG group. No evidence of a significant association between TyG index and CV mortality or all-cause mortality in patients with CAD was identified. Conclusions: The elevated TyG index is a promising predictive factor of adverse cardiovascular events in patients with CAD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021228521.

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

Background: Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis. Methods: A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to collect the qualified studies that analyzed the prognostic value of GDF-15 in CHF from the inception of these online databases to September 25, 2021. The hazard ratio (HR) calculated for logGDF-15 of all-cause death and the related 95% confidence interval (CI) in multivariate analysis were used to measure the effect size. Additionally, subgroup analyses stratified by characteristics of the study participants were conducted for incremental evidence of GDF-15 in CHF with different clinical status. Results: A total of ten eligible studies involving 6,244 CHF patients were finally taken into the quantitative analysis. Results in the random-effects model indicated that there was an increased risk of 6% in all-cause mortality with a per 1LnU increase in baseline GDF-15 concentration (HR: 1.06, 95% CI: 1.03-1.10, P < 0.001). In stratified analyses, the association of GDF-15 with risk of all-cause mortality was found among chronic ischemic HF patients (HR:1.75, 95%CI: 1.24-2.48, P = 0.002), while the association was not found among chronic nonischemic HF patients (HR:1.01, 95%CI: 1.00-1.02, P = 0.219). Conclusion: The elevated GDF-15 is associated with an increased risk of all-cause mortality in CHF, especially, among CHF patients with ischemic etiology. The circulating GDF-15 might be a prognostic indicator in CHF patients. Registration Number: https://www.crd.york.ac.uk/PROSPERO; CRD42020210796.