The neutrophil-to-apolipoprotein A1 ratio is associated with adverse outcomes in patients with acute decompensated heart failure at different glucose metabolic states: a retrospective cohort study.

BACKGROUND: The present study was performed to assess the association between the neutrophil-to-apolipoprotein A1 ratio (NAR) and outcomes in patients with acute decompensated heart failure (ADHF) at different glucose metabolism states. METHODS: We recruited 1233 patients with ADHF who were admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from December 2014 to October 2019. The endpoints were defined as composites of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke and exacerbation of chronic heart failure. The restricted cubic spline was used to determine the best cutoff of NAR, and patients were divided into low and high NAR groups. Kaplan-Meier plots and multivariable Cox proportional hazard models were used to investigate the association between NAR and the risk of adverse outcomes. RESULTS: During the five-year follow-up period, the composite outcome occurred in 692 participants (56.1%). After adjusting for potential confounding factors, a higher NAR was associated with a higher incidence of composite outcomes in the total cohort (Model 1: HR = 1.42, 95% CI = 1.22-1.65, P<0.001; Model 2: HR = 1.29, 95% CI = 1.10-1.51, P = 0.002; Model 3: HR = 1.20, 95% CI = 1.01-1.42, P = 0.036). At different glucose metabolic states, a high NAR was associated with a high risk of composite outcomes in patients with diabetes mellitus (DM) (Model 1: HR = 1.54, 95% CI = 1.25-1.90, P<0.001; Model 2: HR = 1.40, 95% CI = 1.13-1.74, P = 0.002; Model 3: HR = 1.31, 95% CI = 1.04-1.66, P = 0.022), and the above association was not found in patients with prediabetes mellitus (Pre-DM) or normal glucose regulation (NGR) (both P>0.05). CONCLUSIONS: The NAR has predictive value for adverse outcomes of ADHF with DM, which implies that the NAR could be a potential indicator for the management of ADHF.

Growth differentiation factor-15 as a negative predictor for microvascular obstruction in ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

Growth differentiation factor-15 (GDF-15) is an anti-inflammatory cytokine with cardioprotective effects, but circulating GDF-15 concentration predicts adverse cardiovascular outcomes in clinical settings. Microvascular obstruction (MVO) formation contributed to poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (pPCI). We aimed to investigate GDF-15 concentration in relation to cardiac magnetic resonance (CMR)-derived MVO in STEMI patients after pPCI, which might help better understand the role of GDF-15 in STEMI. GDF-15 levels at 6 h after pPCI and MVO extent at day 5 ± 2 after pPCI were measured in 74 STEMI patients (mean age 60.3 ± 12.8 years, 86.5% men). The adjusted association of GDF-15 with MVO was analyzed with MVO treated as a categorized variable (extensive MVO, defined as MVO extent ≥ 2.6% of left ventricular (LV)) and a continuous variable (MVO mass, % of LV), respectively, in multivariate logistic and linear regression models. 41.9% of the patients developed extensive MVO after pPCI. In multivariate analysis, the odds ratio (95% confidential interval (CI)) of each standard deviation (SD) increase in GDF-15 for developing extensive MVO was 0.46 (0.21, 0.82), p = 0.02). Consistently, when MVO was used a continuous variable, each SD increase in GDF-15 was associated with a substantially lower MVO mass (ß - 0.42, standard error 0.19, p = 0.03). GDF-15 was a negative predictor for MVO in STEMI patients after pPCI. The observation was consistent with results from experiment studies, suggesting a potential protective effect of GDF-15 against cardiac injury.

Association between the haemoglobin glycation index (HGI) and clinical outcomes in patients with acute decompensated heart failure.

BACKGROUND: A growing number of studies show that people with similar blood glucose levels have different levels of glycosylated haemoglobin (HbA1c), and relying only on HbA1c may lead to clinical decision-making errors. The haemoglobin glycation index (HGI) quantifies the difference in HbA1c among individuals and is strongly linked to the risk of cardiovascular disease. However, the connection between this phenomenon and the poor outcomes of patients with acute decompensated heart failure (ADHF) is currently unknown. PATIENTS AND METHODS: This retrospective, single-centre-based cohort study included 1531 hospitalized patients with ADHF from September 2010 to January 2020. The HGI is calculated from the difference between the observed and predicted HbA1c values [predicted HbA1c = 0.024 × fasting plasma glucose (FPG) (mg/dL)+3.1]. The endpoints examined in the study included all-cause death, cardiovascular (CV) death, and major adverse cardiac events (MACE). We fitted multivariable-adjusted Cox proportional hazard models to investigate the association between the HGI and clinical outcomes. RESULTS: During the five-year follow-up, 427 (27.9%) patients died from all causes, 232 (15.6%) from CV death, and 848 (55.4%) from MACE. The restricted cubic spline analysis also showed that the cumulative risk of all-cause and CV deaths decreased linearly with increasing HGI. According to multivariate Cox proportional hazard models, the highest tertile of the HGI was associated with a lower incidence of all-cause and cardiovascular deaths [all-cause death, adjusted hazard ratio (HR): 0.720, 95% confidence interval (CI): 0.563-0.921, p = 0.009; CV death, adjusted HR: 0.619, 95% CI: 0.445-0.861, p = 0.004]. A 1% increase in the HGI was associated with a 12.5% reduction in the risk of all-cause death and a 20.8% reduction in the risk of CV death. CONCLUSIONS: A high HGI was directly associated with a reduction in all-cause and CV deaths but was not associated with MACE. These findings may be helpful in the management of patients with ADHF.

Recent studies have demonstrated that significant discrepancies between HbA1c and actual blood glucose levels may lead to clinical decision-making errors.The inconsistency of previous research results suggests that the HGI may have different predictive ability in populations with different diseases.

Circulating exosomal mir-16-2-3p is associated with coronary microvascular dysfunction in diabetes through regulating the fatty acid degradation of endothelial cells.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a frequent complication of diabetes mellitus (DM) characterized by challenges in both diagnosis and intervention. Circulating levels of microRNAs are increasingly recognized as potential biomarkers for cardiovascular diseases. METHODS: Serum exosomes from patients with DM, DM with coronary microvascular dysfunction (DM-CMD) or DM with coronary artery disease (DM-CAD) were extracted for miRNA sequencing. The expression of miR-16-2-3p was assessed in high glucose-treated human aortic endothelial cells and human cardiac microvascular endothelial cells. Fluorescence in situ hybridization (FISH) was used to detect miR-16-2-3p within the myocardium of db/db mice. Intramyocardial injection of lentivirus overexpressing miR-16-2-3p was used to explore the function of the resulting gene in vivo. Bioinformatic analysis and in vitro assays were carried out to explore the downstream function and mechanism of miR-16-2-3p. Wound healing and tube formation assays were used to explore the effect of miR-16-2-3p on endothelial cell function. RESULTS: miR-16-2-3p was upregulated in circulating exosomes from DM-CMD, high glucose-treated human cardiac microvascular endothelial cells and the hearts of db/db mice. Cardiac miR-16-2-3p overexpression improved cardiac systolic and diastolic function and coronary microvascular reperfusion. In vitro experiments revealed that miR-16-2-3p could regulate fatty acid degradation in endothelial cells, and ACADM was identified as a potential downstream target. MiR-16-2-3p increased cell migration and tube formation in microvascular endothelial cells. CONCLUSIONS: Our findings suggest that circulating miR-16-2-3p may serve as a biomarker for individuals with DM-CMD. Additionally, miR-16-2-3p appears to alleviate coronary microvascular dysfunction in diabetes by modulating ACADM-mediated fatty acid degradation in endothelial cells.

Platelet mitochondrial DNA methylation: A novel biomarker for myocardial infarction - A preliminary study.

BACKGROUND: Platelet activation and thrombus formation play critical roles in the pathogenesis of myocardial infarction (MI). In addition to their role in energy production, platelet mitochondria also regulate cellular functions related to apoptosis, oxidative stress, and inflammation. Epigenetic modifications of platelet mitochondrial DNA (mtDNA) may influence platelet function and are believed to be an important factor in MI. Therefore, the aim of this study was to investigate the differences in platelet mtDNA methylation levels between MI patients and controls. METHODS: The present study utilized propensity score matching to generate 45 multivariate matched apparently healthy controls for 45 patients with newly-onset acute MI. Platelet mtDNA methylation levels were assessed through bisulfite-PCR pyrosequencing and compared between the two groups, with further adjustments made in the sensitivity analysis. RESULTS: Among the measured mitochondrial genes (MT-COX1, MT-COX2, MT-COX3, MT-ND5, MT-ATP6 and tRNA_Leu), patients with MI exhibited statistically significant differences in mtDNA methylation levels as compared to matched controls. Specifically, higher levels of mtDNA methylation were observed in MT-COX1, MT-COX3, and tRNA_Leu, while a lower level was observed in MT-ATP6 (all p < 0.0001). These results remained robust in the sensitivity analysis. CONCLUSION: Our study demonstrated significant variations in platelet mtDNA methylation levels between patients with MI and controls. Platelet mtDNA methylation may serve as a novel biomarker for MI. This observation also provided some insights into the etiology of MI.

Hypertension-Driven Regulatory T-Cell Perturbations Accelerate Myocardial Ischemia-Reperfusion Injury.

BACKGROUND: Patients with a history of hypertension have elevated inflammation and a worse prognosis after acute myocardial infarction (AMI). Regulatory T cells (Tregs) are reported to lose their immunosuppressive capacity under pathological conditions. However, whether hypertension leads to Treg dysfunction, thus accelerating myocardial ischemia-reperfusion injury, is still unknown. METHODS: Studies were performed in hypertensive rats and mice with myocardial ischemia-reperfusion injury. The frequencies and phenotypes of Tregs were analyzed by flow cytometry and immunohistochemistry. Reconstruction Treg experiments were performed to evaluate the effect of Tregs on ischemia-reperfusion injury. Patients with AMI were enrolled to assess circulating Tregs, inflammatory cytokines, and cardiac function. RESULTS: In this study, we found that hypertension leads to proinflammatory Th1 (T helper 1 cell)-like Treg subsets with compromised suppressive capacity. Reconstruction Treg experiments identified that dysfunctional Tregs induced by hypertension play a pathogenic role in the progression of myocardial ischemia-reperfusion injury. In particular, we identified HDAC6 (histone deacetylase 6) as a central regulator in the perturbed Tregs. Clinical studies revealed that the hypertension-induced reduction in circulating Tregs strongly correlated with the higher occurrence rate of microvascular obstruction in AMI patients with hypertension. CONCLUSIONS: Our study provided promising clues to explain the poor prognosis of hypertensive AMI patients due to alterations in Tregs. Targeting disturbed Tregs may be a new strategy to treat AMI patients with hypertension.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWTPW, RWTIVS+PW and RWTIVS. The included patients were divided according to the median values of RWTPW, RWTIVS+PW, and RWTIVS, respectively. Survival analysis were performed with Kaplan-Meier plot and multivariate Cox proportional hazard model was established to evaluate the adjusted hazard ratio of the three kinds of RWT for all cause death, cardiac death and MACE (major adverse cardiac death). RESULTS: There was no significance for the survival analysis between the low and high groups of RWTPW, RWTIVS+PW and RWTIVS at 30 days and 12 months. Nonetheless, the cumulative incidence of all cause death and cardiac death in the low group of RWTPW and RWTIVS+PW was higher than those in the high group at 60 months. The cumulative incidence of MACE in the low group of RWTPW was higher than the high group at 60 months. Multivariate Cox regression model showed that RWTPW were inversely associated with long-term cardiac death and MACE in STEMI patients. In the subgroup analysis, three calculations of RWT had no predictive value for the patients with anterior myocardial infarction. By contrast, RWTPW was the most stable independent predictor for the long-term outcomes of the patients with non-anterior myocardial infarction. CONCLUSION: RWTPW, RWTIVS+PW and RWTIVS had no predictive value for the long-term clinical outcomes of patients with anterior myocardial infarction, whereas RWTPW was a reliable predictor for all cause death, cardiac death and MACE in patients with non-anterior myocardial infarction.

Empagliflozin ameliorates atherosclerosis via regulating the intestinal flora.

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora. METHODS: Six-week-old male ApoE-/- mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE-/- mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses. RESULTS: In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group. CONCLUSIONS: Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.

Trophoblast Stem-Cell-Derived Exosomes Alleviate Cardiotoxicity of Doxorubicin via Improving Mfn2-Mediated Mitochondrial Fusion.

Doxorubicin (Dox) is an anticancer drug widely used in tumor chemotherapy, but it has the side-effect of cardiotoxicity, which is closely related to mitochondrial damage. Mitochondrial dynamics is a quality control mechanism that usually helps to maintain a healthy mitochondrial pool. Trophoblast stem cell-derived exosomes (TSC-Exos) have been shown to protect cardiomyocytes from DOX-induced cardiotoxicity. To explore whether the cardioprotective role is mediated by the regulation of mitochondrial dynamic mechanism, TSC-Exos were isolated from human trophoblast stem cells by ultracentrifugation and characterized by Western blot and transmission electron microscopy. Cellular experiments of H9c2 cardiomyocytes co-cultured with Dox and TSC-Exos were performed in vitro to determine the levels of reactive oxygen species generation and apoptosis level. An animal model of heart failure was established by intraperitoneal injection of Dox in vivo, therapy mice were received additional intracardiac injection of TSC-Exos, then, the cardiac function, cardiomyocyte apoptosis and mitochondrial fragmentation were ameliorated. Histology assays suggest that Dox caused an increased tendency of mitochondrial fission, which was manifested by a decrease in the average size of mitochondria. By receiving TSC-Exos treatment, this effect was eliminated. In summary, these results suggest that TSC-Exos alleviate DOX-induced cardiotoxicity through antiapoptotic effect and improving mitochondrial fusion with an increase in Mfn2 expression. This study is the first to provide a potential new treatment scheme for the treatment of heart failure from the perspective of the relationship between TSC-Exos and mitochondrial dynamics.

Heart-gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion.

AIMS: Recent studies have suggested a key role of intestinal microbiota in pathological progress of multiple organs via immune modulation. However, the interactions between heart and gut microbiota remain to be fully elucidated. The aim of the study is to investigate the role of gut microbiota in the post-ischaemia/reperfusion (I/R) inflammatory microenvironment. METHODS AND RESULTS: Here, we conducted a case-control study to explore the association of gut bacteria translocation products with inflammation biomarkers and I/R injury severity in ST-elevation myocardial infarction patients. Then, we used a mouse model to determine the effects of myocardial I/R injury on gut microbiota dysbiosis and translocation. Blooming of Proteobacteria was identified as a hallmark of post-I/R dysbiosis, which was associated with gut bacteria translocation. Abrogation of gut bacteria translocation by antibiotic cocktail alleviated myocardial I/R injury via mitigating excessive inflammation and attenuating myeloid cells mobilization, indicating the bidirectional heart-gut-microbiome-immune axis in myocardial I/R injury. Glucagon-like peptide 2 (GLP-2), an endocrine peptide produced by intestinal L-cells, was used in the experimental myocardial I/R model. GLP-2 administration restored gut microbiota disorder and prevented bacteria translocation, eventually attenuated myocardial I/R injury through alleviating systemic inflammation. CONCLUSION: Our work identifies a bidirectional communication along the heart-gut-microbiome-immune axis in myocardial I/R injury and demonstrates gut bacteria translocation as a key regulator in amplifying inflammatory injury. Furthermore, our study sheds new light on the application of GLP-2 as a promising therapy targeting gut bacteria translocation in myocardial I/R injury.

A reduction of Syndecan-4 in macrophages promotes atherosclerosis by aggravating the proinflammatory capacity of macrophages.

BACKGROUND: Cardiovascular diseases (CVDs) are a significant cause of mortality worldwide and are characterized by severe atherosclerosis (AS) in patients. However, the molecular mechanism of AS formation remains elusive. In the present study, we investigated the role of syndecan-4 (SDC4), a member of the syndecan family, in atherogenesis. METHODS AND RESULTS: The expression of SDC4 decreased in mouse severe AS models. Moreover, knockout of SDC4 accelerated high-cholesterol diets (HCD)-induced AS in ApoE-/- mice. Mechanistically, the decrease of SDC4 increased macrophage proinflammatory capacity may be through the PKCα-ABCA1/ABCG1 signaling pathway. CONCLUSION: These findings provide evidence that SDC4 reduction links macrophages and inflammation to AS and that SDC4 in macrophages provides a therapeutic target for preventing AS formation.

Prognostic value of triglyceride glucose (TyG) index in patients with acute decompensated heart failure.

BACKGROUND: The triglyceride glucose (TyG) index has been proposed as a reliable marker of insulin resistance (IR) and an independent predictor of cardiovascular disease risk. However, its prognostic value in patients with acute decompensated heart failure (ADHF) remains unclear. METHODS: A total of 932 hospitalized patients with ADHF from January 1st, 2018 to February 1st, 2021 were included in this retrospective study. The TyG index was calculated as ln [fasting triglyceride level (mg/dL) × fasting plasma glucose level (mg/dL)/2]. Patients were divided into tertiles according to TyG index values. The primary endpoints were all-cause death, cardiovascular (CV) death and major adverse cardiac and cerebral events (MACCEs) during follow-up. We used multivariate adjusted Cox proportional hazard models and restricted cubic spline analysis to investigate the associations of the TyG index with primary endpoints. RESULTS: During a median follow-up time of 478 days, all-cause death, CV death and MACCEs occurred in 140 (15.0%), 103 (11.1%) and 443 (47.9%) cases, respectively. In multivariate Cox proportional hazard models, the risk of incident primary endpoints was associated with the highest TyG tertile. After adjustment for confounding factors, hazard ratios (HRs) for the highest tertile (TyG index ≥ 9.32) versus the lowest tertile (TyG index < 8.83) were 2.09 (95% confidence interval [CI], 1.23-3.55; p = 0.006) for all-cause death, 2.31 (95% CI, 1.26-4.24; p = 0.007) for CV death and 1.83 (95% CI, 1.18-3.01; p = 0.006) for MACCEs. Restricted cubic spline analysis also showed that the cumulative risk of primary endpoints increased as TyG index increased. When the TyG index was used as a continuous variable, the hazard ratios of the three primary endpoints rapidly increased within the higher range of the TyG index (all cause death, TyG > 9.08; CV death, TyG > 9.46; MACCEs, TyG > 9.87). CONCLUSIONS: The elevated TyG index was independently associated with poor prognosis, and thus would be useful in the risk stratification in patients with ADHF.

Early and midterm outcomes of transcatheter aortic-valve replacement with balloon-expandable versus self-expanding valves: A meta-analysis.

BACKGROUND: Current guidelines provide recommendation for transcatheter aortic-valve replacement (TAVR) in severe aortic stenosis without emphasis on valve systems. The comparative performances of balloon-expandable valves (BEV) and self-expanding valves (SEV) remain unclear. We aim to compare the early (30-day) and midterm (1-year) mortality and cardiovascular outcomes of BEV with SEV. METHODS: PubMed, CENTRAL, and EMBASE were searched from inception to February 13, 2020 for randomized controlled trials (RCTs) and propensity-score matched (PSM) studies. Odds ratios (ORs) for binary outcomes and mean differences for continuous outcomes were pooled using random-effect models (DerSimonian-Laird method) with Hartung-Knapp-Sidik-Jonkman variance correction. Primary outcomes were early and midterm all-cause mortality. RESULTS: We included 3 RCTs (1418 patients) and 12 PSM studies (36,540 patients). Compared with SEV, BEV was associated with significantly lower mortality at 30 days (OR 0.76, 95% CI 0.67-0.85, p < 0.001, I2 = 0) and 1 year (OR 0.87, 95% CI 0.77-0.99, p = 0.04, I2 = 20.4%) in PSM studies, but not RCTs with insufficient power. Similar findings were found in subgroups analysis based on valve generations and SEV types. The 30-day and 1-year cardiovascular mortality, 30-day incidences of moderate to severe paravalvular leak, procedural contrast agent volume, and procedure time were lower, but transvalvular pressure gradient was higher in BEV than SEV in PSM studies. The 30-day incidences of permanent pacemaker implantation (PPI), acute kidney injury, stroke, major bleeding, major vascular complications, and rehospitalization were not statistically different between BEV and SEV. Early-generation SEV was associated with a higher 30-day PPI risk than corresponding BEV comparators. PPI risk was lower in ACURATE neo (Boston Scientific, Natick, MA) but higher in Evolut R SEV (Medtronic Inc., Minneapolis, MN), both compared with SAPIEN 3 BEV (Edwards Lifesciences, Irvine, CA). CONCLUSIONS: PSM studies suggest lower early and midterm mortality in BEV than SEV, but the contribution of unmeasured confounders cannot be excluded. Results from adequately powered RCTs with long-term follow-up are critically needed to confirm these findings.

A reduction in the vascular smooth muscle cell focal adhesion component syndecan-4 is associated with abdominal aortic aneurysm formation.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a serious vascular disease for which there is no effective drug treatment. The incidence of AAA increases significantly as a subject ages, and the molecular mechanism of AAA formation remains elusive. In the present study, we investigated the role of syndecan-4 (SDC4), an important component of focal adhesions, in AAA formation and its association with phenotypic changes in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: The protein expression levels of SDC4 were significantly decreased in human AAA tissue and those of an AAA mouse model. Moreover, SDC4 knockout (KO) in mice accelerated the formation and rupture of AAAs induced by angiotensin II (Ang II) and calcium chloride (CaCl2 ) Mechanistically, the decrease in SDC4 led to the transformation of cultured VSMCs from a contractile to a secretory phenotype. The RhoA-F/G-actin-myocardin-related transcription factor-A (MRTF-A) signalling pathway was shown to be involved in SDC4-dependent VSMC alteration. Sphingosine-1-phosphate (S1P), a G-protein-coupled receptor, attenuated the AAA formation in SDC4-KO and wild-type (WT) mice in response to Ang II and CaCl2 stimulation. CONCLUSION: We herein demonstrated that silencing SDC4 was associated with increased AAA formation and phenotypic changes in VSMCs via the RhoA-F/G-actin-MRTF-A pathway. These findings indicated that a reduction in SDC4 expression was an important pathological alteration and potential therapeutic target for AAA formation.

The transcriptome of circulating cells indicates potential biomarkers and therapeutic targets in the course of hypertension-related myocardial infarction.

Hypertension (HT) is the most common public-health challenge and shows a high incidence around the world. Cardiovascular diseases are the leading cause of mortality and morbidity among the elderly (age > 65 years) in the United States. Now, there is widespread acceptance of the causal link between HT and acute myocardial infarction (MI). This is the first data-mining study to identify co-expressed differentially expressed genes (co-DEGs) between HT and MI (relative to normal control) and to uncover potential biomarkers and therapeutic targets of HT-related MI. In this manuscript, HT-specific DEGs and MI-specific DEGs and differentially expressed microRNAs (DE-miRNAs) were identified in Gene Expression Omnibus (GEO) datasets GSE24752, GSE60993, GSE62646, and GSE24548 after data consolidation and batch correction. Subsequently, enrichment in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways as well as protein-protein interaction networks were identified, and single-gene gene set enrichment analysis was performed to determine the affected biological categories and networks. Cross-matching of the results on co-DE-miRNAs and predicted miRNAs targeting the co-DEGs was conducted and discussed as well. We found that MYC and HIST1H2BO may be associated with HT, whereas FCGR1A, FYN, KLRD1, KLRB1, and FOLR3 may be implicated in MI. Moreover, co-DEGs FOLR3 and NFE2 with predicted miRNAs and DE-miRNAs, especially miR-7 and miR-548, may be significantly associated and show huge potential as a new set of novel biomarkers and important molecular targets in the course of HT-related MI.

High-mobility group box-1 promotes vascular calcification in diabetic mice via endoplasmic reticulum stress.

Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High-mobility group box-1 (HMGB-1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB-1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB-1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4-phenylbutyrate (4-PBA). Mineral deposition was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT-PCR. Expression and location of HMGB-1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB-1 expression, ERS and vascular calcification. However, inhibition of HMGB-1 with Gly or inhibition of ERS with 4-PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB-1 attenuated advanced glycation end products (AGEs)-induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB-1 in VSMCs, which was reversed by 4-PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB-1 and AGEs. However, inhibition of ERS with 4-PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB-1. Thus, diabetes induced translocation and secretion of HMGB-1 via ERS, which resulted in calcification in diabetic mice and in AGEs-treated VSMCs.

The diagnostic capability of electrocardiography on the cardiogenic shock in the patients with acute myocarditis.

BACKGROUND: The study was performed to assess the diagnostic capability of ECG on the cardiogenic shock (CS) in acute myocarditis. A new score was derived from the combination of the ECG parameters and the diagnostic value was also evaluated. METHODS: Total 103 consecutive patients with acute myocarditis admitted in Nanjing Drum Hospital were enrolled in the current study. The cohort was divided into fulminant myocarditis group (FM, n = 20) and non fulminant myocarditis group (NFM, n = 83). The demographic features, results of electrocardiography (ECG) and ultracardiography were compared. Logistic regression analysis was conducted to identify the relevant factors in ECG parameters. We created a new variable called "ECG score" by certain combination of ECG parameters. The diagnostic capability of ECG score for CS was compared with the existing diagnostic indices using regression model and receiver-operating characteristics (ROC) analysis. RESULTS: There were several changes on ECG significantly different between the two groups. Multivariate regression analysis demonstrated PR + QRS interval (P = 0.008), ventricular arrhythmia (P = 0.001) and pathological Q wave (P = 0.003) were the independent relevant factors of CS. The derived variable "ECG score" was identified as a significant relevant factor of CS by multivariate regression model. ROC analysis showed PR + QRS interval, ventricular arrhythmia and pathological Q wave all had equivalent diagnostic capability to left ventricular ejection fraction (LVEF) and shock index (SI). ECG score was equivalent to LVEF but superior to SI in diagnosing CS CONCLUSIONS: ECG was valuable in diagnosing CS due to acute myocarditis. The ECG score was superior to the traditional diagnostic indices and could be used for an rapid recognition of CS.

Predictive Value of Fasting Blood Glucose for Microvascular Obstruction in Nondiabetic Patients with ST-Segment Elevation Myocardial Infarction after Primary Percutaneous Coronary Intervention.

BACKGROUND: The relationship between fasting blood glucose (FBG) and microvascular obstruction (MVO) after primary percutaneous coronary intervention (PCI) remains unclear in nondiabetic patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to determine the predictive value of FBG in MVO in nondiabetic STEMI patients. METHODS: A total of 108 nondiabetic STEMI patients undergoing primary PCI were enrolled in this study. The patients were classified into either the MVO group or non-MVO group based on cardiac magnetic resonance imaging (CMR). RESULTS: FBG in the MVO group was higher than in the non-MVO group. Univariate analysis showed that FBG, peak high-sensitive troponin T (TnT), pre-PCI thrombolysis in myocardial infarction (pre-PCI TIMI) flow, left ventricular ejection fraction (LVEF), infarction size, left ventricular end-diastolic diameter (LVEDd), left ventricular end-diastolic volume (LVEDV), and global longitudinal strain (GLS) were likely predictive factors of MVO. After adjustment for other parameters, FBG, peak TnT, LVEF, and LVEDV remained independent predictors for MVO. CONCLUSION: FBG was independently associated with MVO in nondiabetic STEMI patients.

Extracellular vesicles derived from Krüppel-Like Factor 2-overexpressing endothelial cells attenuate myocardial ischemia-reperfusion injury by preventing Ly6Chigh monocyte recruitment.

Background: The ischemia/reperfusion (I/R) process in patients with ST-segment elevation myocardial infarction (STEMI) triggers an immune response, resulting in myocyte death. Krüppel-Like Factor 2 (KLF2), which is highly expressed in endothelial cells (ECs) under laminar flow, exerts anti-inflammatory effects. In this study, we explored the role of small extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in the immunomodulation and its implications in myocardial I/R injury. Methods and Results: The small EVs were isolated from KLF2-overexpressing ECs' supernatant using gradient centrifugation. Mice were subjected to 45 min of ischemia followed by reperfusion, and KLF2-EVs were administrated through intravenous injection. KLF2-EVs ameliorated I/R injury and alleviated inflammation level in the serum and heart. We employed the macrophage depletion model and splenectomy and showed that Ly6Chigh monocyte recruitment from bone marrow was the main target of KLF2-EVs. miRNA-sequencing of KLF2-EVs and bioinformatics analysis implicated miRNA-24-3p (miR-24-3p) as a potent candidate mediator of monocyte recruitment and CCR2 as a downstream target. miR-24-3p mimic inhibited the migration of Ly6Chigh monocytes, and miR-24-3p antagomir reversed the effect of KLF2-EVs in myocardial I/R. Conclusion: Our data demonstrated that KLF2-EVs attenuated myocardial I/R injury in mice via shuttling miR-24-3p that restrained the Ly6Chigh monocyte recruitment. Thus, KLF2-EVs could be a potential therapeutic agent for myocardial I/R injury.

Short-term and long-term outcomes of bailout versus planned coronary rotational atherectomy.

The goal of this study was to compare in-hospital and long-term events between bailout rotational atherectomy (RA) and planned RA. In this retrospective study, All patients who underwent percutaneous coronary intervention (PCI) using RA at Nanjing Drum Tower Hospital from November 2011 to December 2018 were enrolled in this study. Planned RA was defined as RA performed immediately before balloon pre-dilation, while bailout RA was defined as RA after failure to expand the balloon or perform any other procedure. In-hospital and long-term major adverse cardiac events (MACE, defined as cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR) and stroke) were compared between the two groups. After statistical analysis, a total of 211 patients underwent PCI with RA during the study period: 153 in the planned RA group, and 58 in the bailout group. The incidence of coronary dissection was significantly higher in the bailout RA group than in the planned RA group (22.4% vs. 6.5%, P = 0.001). However, no significant difference in in-hospital MACE was found between the two groups (12.1% vs. 13.7%, P = 0.752). There was no difference in all-cause mortality (9.1% vs. 12.5%, P = 0.504) or long-term MACE (13.8% vs. 17.1%, P = 0.560) between the groups. Bailout RA was associated with a significantly longer procedural time (139.86 ± 56.24 min vs. 105.56 ± 36.71 min, P < 0.001) than planned RA. Therefore, compared with bailout RA, planned RA is associated with shorter procedural time and reduced incidence of coronary dissection, with no difference in MACE or mortality.