The association between triglyceride-glucose index and related parameters and risk of cardiovascular disease in American adults under different glucose metabolic states.

BACKGROUND: Cardiovascular disease (CVD) encompasses an array of cardiac and vascular disorders, posing a significant threat to global health. It remains unclear whether there exists an association between triglyceride-glucose index (TyG) and its derived indices and the incidence of cardiovascular disease, and in particular, the strength of the association in populations with different glucose metabolisms is not known. METHODS: Data extracted from the National Health and Nutrition Examination Survey (NHANES) covering the period from 1999 to 2020, involving a cohort of 14,545 participants, were leveraged for the analysis. Statistical assessments were executed utilizing R software, employing multivariable logistic regression models to scrutinize the correlation between TyG and its associated parameters with the incidence of cardiovascular disease across diverse glucose metabolism categories. Interaction analyses and restricted cubic splines were applied to evaluate potential heterogeneity in associations and investigate the link between TyG and its derivatives with the occurrence of cardiovascular disease. Furthermore, receiver operating characteristic curves were constructed to evaluate the extent of variability in the predictive performance of TyG and its derived parameters for cardiovascular disease across distinct glucose metabolic statuses. RESULTS: This study found that TyG and its related parameters were differentially associated with the occurrence of cardiovascular disease in different glucose metabolic states. Curvilinear correlations were found between TyG in the IFG population and TyG-WC, TyG-BMI, and TyG-WHtR in the impaired glucose tolerance (IGT) population with the occurrence of cardiovascular disease. In addition, the introduction of TyG and its derived parameters into the classical Framingham cardiovascular risk model improved the predictive performance in different glucose metabolism populations. Among them, the introduction of TyG-WHtR in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), IFG & IGT and diabetes groups and TyG in the IGT group maximized the predictive power. CONCLUSIONS: The findings provide new insights into the relationship between the TyG index and its derived parameters in different glucose metabolic states and the risk of cardiovascular disease, offering important reference value for future clinical practice and research. The study highlights the potential for improved risk stratification and prevention strategies based on TyG and its derived parameters.

The role of circulating biomarkers in predicting the 30-day mortality of immune checkpoint inhibitors-related myocarditis: a retrospective cohort study.

Immune checkpoint inhibitors-related myocarditis (ICIs-M) is a rare and highly lethal immune-related adverse events (irAEs) in common irAEs. This study aims to find circulating biomarkers that can reflect disease state and prognosis accurately. 48 patients with ICIs-M were enrolled according to the diagnostic criteria for ICIs-related myocarditis. For all enrolled patients, valuable information was extracted retrospectively from the medical system, mainly including demographic information, tumor information and laboratory examination. The follow-up period was defined as 30 days after the first diagnosis of ICIs-M. In this study, the 30-day mortality rate of ICIs-M was 24.4%. After adjusting for potential confounding factors using multivariate analysis tools, we demonstrated the excellent performance of biomarkers in predicting 30-day mortality in patients with ICIs-M, including PLT (hazard ratio (HR), 1.07; 95% confidence interval (95%CI), 1.01-1.14; p = 0.028), ALT (HR, 1.23; 95%CI, 1.06-1.41; p = 0.005), AST(HR, 1.06; 95%CI, 1.01-1.10; p = 0.015), LDH (HR, 1.15; 95%CI, 1.04-1.26; p = 0.004), troponin I(HR, 1.44; 95%CI, 1.09-1.89; p = 0.009), PLR (blood plate/lymphocyte) (HR, 1.04; 95% CI, 1.01-1.07; p = 0.024), LAR (lactate dehydrogenase/albumin) (HR, 1.05; 95%CI, 1.01-1.09; p = 0.012), and AAR (aspartate transaminase/albumin) (HR, 1.18; 95%CI, 1.00-1.39; p = 0.048). The analysis of the receiver operating characteristic showed that biomarkers with area under curve (AUC) greater than or equal to 0.80 were LDH (cutoff value, 724.5; AUC, 0.86; 95%CI, 0.75-0.97), LAR (cutoff value, 18.11; AUC, 0.87; 95%CI, 0.76-0.97), troponin I (cutoff value, 0.87; AUC, 0.80; 95%CI, 0.62-0.99), and AAR(cutoff value, 1.52; AUC, 0.80; 95%CI, 0.61-0.98). LDH, LAR, troponin I, and AAR are a group of promising biomarkers that demonstrate excellent predictive ability in predicting the 30-day mortality rate of immune-related myocarditis.

Ultrasound-guided periadventitial administration of rapamycin-fibrin glue attenuates neointimal hyperplasia in the rat carotid artery injury model.

INTRODUCTION: Arterial restenosis caused by intimal hyperplasia (IH) is a serious complication after vascular interventions. In the rat carotid balloon injury model, we injected phosphate buffer saline (PBS), rapamycin-phosphate buffer saline suspension (RPM-PBS), blank fibrin glue (FG) and rapamycin-fibrin glue (RPM-FG) around the injured carotid artery under ultrasound guidance and observed the inhibitory effect on IH. METHODS: The properties of RPM-FG in vitro were verified by scanning electron microscopy (SEM) and determination of the drug release rate. FG metabolism in vivo was observed by fluorescence imaging. The rat carotid balloon injury models were randomly classified into 4 groups: PBS group (control group), RPM-PBS group, FG group, and RPM-FG group. Periadventitial administration was performed by ultrasound-guided percutaneous puncture on the first day after angioplasty. Carotid artery specimens were analyzed by immunostaining, Evans blue staining and hematoxylin-eosin staining. RESULTS: The RPM particles showed clustered distributions in the FG block. The glue was maintained for a longer time in vivo (> 14 days) than in vitro (approximately 7 days). Two-component liquid FG administered by ultrasound-guided injection completely encapsulated the injured artery before coagulation. The RPM-FG inhibited IH after carotid angioplasty vs. control and other groups. The proliferation of vascular smooth muscle cells (VSMCs) was significantly inhibited during neointima formation, whereas endothelial cell (EC) repair was not affected. CONCLUSION: Periadventitial delivery of RPM-FG contributed to inhibiting IH in the rat carotid artery injury model without compromising re-endothelialization. Additionally, FG provided a promising platform for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.

Neutrophil membrane-camouflaged nanoparticles alleviate inflammation and promote angiogenesis in ischemic myocardial injury.

Acute myocardial infarction (AMI) induces a sterile inflammatory response, leading to cardiomyocyte damage and adverse cardiac remodeling. Interleukin-5 (IL-5) plays an essential role in developing eosinophils (EOS), which are beneficial for the resolution of inflammation. Furthermore, the proangiogenic properties of IL-5 also contribute to tissue healing following injury. Therefore, targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI. It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose. In this study, we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane. The administration of neutrophil membrane-camouflaged nanoparticles (NM-NPIL-5) in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium, thereby limiting adverse cardiac remodeling after AMI. Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil "decoys" to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their "parent" neutrophils. Finally, the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function. Our findings provided a promising cardiac detoxification agent for acute cardiac injury.

Screening and Bioinformatics Analysis of Crucial Gene of Heart Failure and Atrial Fibrillation Based on GEO Database.

Background and objectives: In clinical practice, we observed that the prognoses of patients with heart failure and atrial fibrillation were worse than those of patients with only heart failure or atrial fibrillation. The study aims to get a better understanding of the common pathogenesis of the two diseases and find new therapeutic targets. Materials and Methods: We downloaded heart failure datasets and atrial fibrillation datasets from the gene expression omnibus database. The common DEGs (differentially expressed genes) in heart failure and atrial fibrillation were identified by a series of bioinformatics methods. To better understand the functions and possible pathways of DEGs, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: We identified 22 up-regulated genes and 14 down-regulated genes in two datasets of heart failure and 475 up-regulated and 110 down-regulated genes in atrial fibrillation datasets. In addition, two co-upregulated (FRZB, SFRP4) and three co-downregulated genes (ENTPPL, AQP4, C1orf105) were identified. GO enrichment results showed that these common differentially expressed genes were mainly concentrated in the signal regulation of the Wnt pathway. Conclusions: We found five crucial genes in heart failure and atrial fibrillation, which may be potential therapeutic targets for patients with heart failure and atrial fibrillation.

Decoy Exosomes Offer Protection Against Chemotherapy-Induced Toxicity.

Cancer patients often face severe organ toxicity caused by chemotherapy. Among these, chemotherapy-induced hepatotoxicity and cardiotoxicity are the main causes of death of cancer patients. Chemotherapy-induced cardiotoxicity even creates a new discipline termed "cardio-oncology". Therefore, relieving toxicities induced by chemotherapy has become a key issue for improving the survival and quality of life in cancer patients. In this work, mesenchymal stem cell exosomes with the "G-C" abundant tetrahedral DNA nanostructure (TDN) are modified to form a decoy exosome (Exo-TDN). Exo-TDN reduces DOX-induced hepatotoxicity as the "G-C" base pairs scavenge DOX. Furthermore, Exo-TDN with cardiomyopathic peptide (Exo-TDN-PCM) is engineered for specific targeting to cardiomyocytes. Injection of Exo-TDN-PCM significantly reduces DOX-induced cardiotoxicity. Interestingly, Exo-TDN-PCM can also promote macrophage polarization into the M2 type for tissue repair. In addition, those decoy exosomes do not affect the anticancer effects of DOX. This decoy exosome strategy serves as a promising therapy to reduce chemo-induced toxicity.

A Novel Compound, Tanshinol Borneol Ester, Ameliorates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Oxidative Stress via the mTOR/ß-TrCP/NRF2 Pathway.

Tanshinol borneol ester (DBZ) exerts anti-atherosclerotic and anti-inflammatory effects. However, its effects on cardiac hypertrophy are not well understood. In this work, we investigated the treatment effects and potential mechanisms of DBZ on the hypertrophic heart under oxidative stress and endoplasmic reticulum (ER) stress. A hypertrophic model was established in rats using transverse-aortic constriction (TAC) surgery and in neonatal rat cardiomyocytes (NRCMs) using angiotensin II (Ang II). Our results revealed that DBZ remarkably inhibited oxidative stress and ER stress, blocked autophagy flow, and decreased apoptosis in vivo and in vitro through nuclear NRF2 accumulation, and enhanced NRF2 stability via regulating the mTOR/ß-TrcP/NRF2 signal pathway. Thus, DBZ may serve as a promising therapeutic for stress-induced cardiac hypertrophy.

Dysregulation of miR-342-3p in plasma exosomes derived from convalescent AMI patients and its consequences on cardiac repair.

Plasma exosomes derived from healthy people have been shown to be beneficial in terms of protecting against ischemia-reperfusion injury or acute myocardial infarction (AMI). However, a pathological condition may severely affect the constitution and biological activity of exosomes. In our study, we isolated plasma exosomes from healthy volunteers and convalescent AMI patients (3-7 d after onset). Compared to exosomes from healthy controls (Nor-Exo), exosomes from convalescent AMI patients (AMI-Exo) exhibited an impaired ability to repair damaged cardiomyocytes both in vitro and in vivo. miRNA sequencing and PCR analysis indicated that miR-342-3p was significantly downregulated in AMI-Exo. Moreover, miR-342-3p alleviated H2O2-induced injury and reduced apoptosis and autophagy in H9c2 cardiomyocytes, while in vivo restoration of miR-342-3p expression enhanced the reparative function of AMI-Exo. Further mechanistic studies revealed that the SOX6 and TFEB genes were two direct and functional targets of miR-342-3p. Taken together, during the early convalescent phase after AMI, dysregulated miR-342-3p in plasma exosomes might be responsible for their impaired cardioprotective potential. miR-342-3p contributed to exosome-mediated heart repair by inhibiting cardiomyocyte apoptosis and autophagy through targeting SOX6 and TFEB, respectively. Our work provided novel insights on the role of plasma exosomes in the natural process of cardiac repair after AMI and suggestions for therapy development.

Exosome-eluting stents for vascular healing after ischaemic injury.

Drug-eluting stents implanted after ischaemic injury reduce the proliferation of endothelial cells and vascular smooth muscle cells and thus neointimal hyperplasia. However, the eluted drug also slows down the re-endothelialization process, delays arterial healing and can increase the risk of late restenosis. Here we show that stents releasing exosomes derived from mesenchymal stem cells in the presence of reactive oxygen species enhance vascular healing in rats with renal ischaemia-reperfusion injury, promoting endothelial cell tube formation and proliferation, and impairing the migration of smooth muscle cells. Compared with drug-eluting stents and bare-metal stents, the exosome-coated stents accelerated re-endothelialization and decreased in-stent restenosis 28 days after implantation. We also show that exosome-eluting stents implanted in the abdominal aorta of rats with unilateral hindlimb ischaemia regulated macrophage polarization, reduced local vascular and systemic inflammation, and promoted muscle tissue repair.

Effects of sacubitril/valsartan on clinical symptoms, echocardiographic parameters, and outcomes in HFrEF and HFmrEF patients with coronary heart disease and chronic kidney disease.

OBJECTIVE: To compare the effects of Angiotensin Receptor-Neprilysin inhibitor (ARNI) on the clinical symptoms, echocardiographic parameters, and outcomes (cardiovascular death and hospitalization) in heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF) patients with coronary heart disease and chronic kidney disease. METHOD: A retrospective observational study was conducted from January 2018 to May 2019, with a follow-up period of 95.4 ± 57.8 days (8 months). Data from 127 patients were included. RESULTS: A statistically significant increase of 68.8% was observed in left ventricular ejection fraction (LVEF) in HFrEF patients compared to that in HFmrEF patients, with an increase of 27.2% at 8 months of follow-up. Sacubitril/valsartan significantly reduced left ventricular end-systolic volumes (LVESV) in HFrEF patients unlike in HFmrEF patients. The decrease in LVESV was 28.8% in HFrEF patients and 17.1% in HFmrEF patients. A significant reduction in the prevalence of severe secondary mitral regurgitation (EROA > 0.4 cm2) was observed in HFrEF compared to that in HFmrEF patients with the use of sacubitril/valsartan. A reduction of 15.6% was observed in HFrEF patients, whereas a reduction of 7.1% was observed in HFmrEF patients. Improvement in functional classification (NYHA) was observed during follow-up. The prevalence of (NYHA III) reduced from 50% to 15.7% in HFrEF patients, whereas a reduction from 21.1% to 8.8% was observed in HFmrEF patients. There was a significant reduction in NT-proBNP in HFrEF patients compared to that in HFmrEF patients. A reduction of 52% was observed in HFrEF patients, whereas a reduction of 28.7% was observed in HFmrEF pateints. Sacubitril/valsartan reduced primary endpoint events in both groups. The prevalence of HF-related hospitalization was higher in HFrEF than in HFmrEF patients: 12.1% vs 7.5%, respectively. The prevalence of CV death in HFrEF vs HFmrEF patients was 3.7% vs 0.5%, respectively. Cardiovascular (CV) death was higher in patients with atrial fibrillation in both groups. CONCLUSION: Sacubitril/valsartan significantly improved morphofunctional remodeling parameters and clinical symptoms in HFrEF patients than in HFmrEF patients.

Small but significant: Insights and new perspectives of exosomes in cardiovascular disease.

Cardiovascular diseases (CVDs) are a major health problem worldwide, and health professionals are still actively seeking new and effective approaches for CVDs treatment. Presently, extracellular vesicles, particularly exosomes, have gained its popularity for CVDs treatment because of their function as messengers for inter- and extra-cellular communications to promote cellular functions in cardiovascular system. However, as a newly developed field, researchers are still trying to fully understand the role of exosomes, and their mechanism in mediating cardiac repair process. Therefore, a comprehensive review of this topic can be timely and favourable. In this review, we summarized the basic biogenesis and characterization of exosomes and then further extended the focus on the circulating exosomes in cellular communication and stem cell-derived exosomes in cardiac disease treatment. In addition, we covered interactions between the heart and other organs through exosomes, leading to the diagnostic characteristics of exosomes in CVDs. Future perspectives and limitations of exosomes in CVDs were also discussed with a special focus on exploring the potential delivery routes, targeting the injured tissue and engineering novel exosomes, as well as its potential as one novel target in the metabolism-related puzzle.

An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs.

Cell therapy has been a promising strategy for cardiac repair after injury or infarction; however, low retention and engraftment of transplanted cells limit potential therapeutic efficacy. Seeding scaffold material with cells to create cardiac patches that are transplanted onto the surface of the heart can overcome these limitations. However, because patches need to be freshly prepared to maintain cell viability, long-term storage is not feasible and limits clinical applicability. Here, we developed an off-the-shelf therapeutic cardiac patch composed of a decellularized porcine myocardial extracellular matrix scaffold and synthetic cardiac stromal cells (synCSCs) generated by encapsulating secreted factors from isolated human cardiac stromal cells. This fully acellular artificial cardiac patch (artCP) maintained its potency after long-term cryopreservation. In a rat model of acute myocardial infarction, transplantation of the artCP supported cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function. The safety and efficacy of the artCP were further confirmed in a porcine model of myocardial infarction. The artCP is a clinically feasible, easy-to-store, and cell-free alternative to myocardial repair using cell-based cardiac patches.

Evaluation of Mechanical Performances of Stents with 38 mm Length in Long Lesion.

OBJECTIVE: Single stent with 38 mm length has emerged as a potential solution for long lesion treatment using PCI. However, long stents need to come over a longer lesion length combined with a higher incidence of tortuous calcification, requiring a stent to provide superior transport and compliance and reduce elastic retraction. Here, we evaluated the mechanical performances of the existing four types of drug eluting stents with 38 mm length, which could provide guidance for clinicians to choose the proper stents for the patients. METHODS: The stents with 38 mm length from XIENCE Xpedition (Abbott, US), SYNERGY (Boston Scientific, US), FIREHAWK (Microport, China), and HELIOS (HELIOS, China) were collected. Mechanical parameters of stents including crossing ability, compliance, elastic recoil, and longitudinal strength were performed. RESULTS: The resistance force of stents from XIENCE Xpedition was smaller than FIREHAWK (p < 0.05), which indicates that the stent from XIENCE Xpedition has better crossing ability. The ratio of stent diameter reduction from both XIENCE Xpedition and SYNERGY was less than 3% with no statistical difference. In addition, the elastic recoil percentage of stents from SYNERGY, XIENCE Xpedition, FIREHAWK, and HELIOS was 1.16%, 2.62%, 3.66%, and 4.19%, respectively, indicating that SYNERGY had better elastic recoil compared to FIREHAWK and HELIOS (p < 0.05), which indicates that the stent from XIENCE Xpedition has better crossing ability. The ratio of stent diameter reduction from both XIENCE Xpedition and SYNERGY was less than 3% with no statistical difference. In addition, the elastic recoil percentage of stents from SYNERGY, XIENCE Xpedition, FIREHAWK, and HELIOS was 1.16%, 2.62%, 3.66%, and 4.19%, respectively, indicating that SYNERGY had better elastic recoil compared to FIREHAWK and HELIOS (p < 0.05), which indicates that the stent from XIENCE Xpedition has better crossing ability. The ratio of stent diameter reduction from both XIENCE Xpedition and SYNERGY was less than 3% with no statistical difference. In addition, the elastic recoil percentage of stents from SYNERGY, XIENCE Xpedition, FIREHAWK, and HELIOS was 1.16%, 2.62%, 3.66%, and 4.19%, respectively, indicating that SYNERGY had better elastic recoil compared to FIREHAWK and HELIOS (. CONCLUSION: The evaluation of mechanical properties for the stent with 38 mm length including crossing ability, compliance, elastic recoil, and longitudinal strength could provide reference index for more accurately clinical application for long lesion treatment.

Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs.

Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. Methods: We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon. Results: Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior. Conclusion: Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.

Circulating tumor cells exit circulation while maintaining multicellularity, augmenting metastatic potential.

Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate and whether multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use in vivo zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do so as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumors at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.This article has an associated First Person interview with the first author of the paper.

Indirect comparison of novel Oral anticoagulants among Asians with non-Valvular atrial fibrillation in the real world setting: a network meta-analysis.

BACKGROUND: The development of novel oral anticoagulants (NOACs) has changed the landscape of non-valvular atrial fibrillation (NVAF) management. In this study, the effectiveness and the safety of several NOACs were evaluated in a real-world setting among Asian patients with NVAF. METHODS: The literature search was conducted crossing different databases including Embase, MEDLINE, and the Cochrane Library from inception through March 1, 2019, for studies which included real-world perspectives comparing the individual NOACs with each other or with warfarin among Asians with NVAF. The primary outcomes were defined as stroke or systemic embolism (SSE) and major bleeding; ischemic stroke, all-cause death as well as intracranial bleeding were classified as the secondary outcomes. RESULTS: From sixteen real-world studies, a total of 312,827 Asian patients were included in this analysis. In comparison with warfarin, the utilization of apixaban, dabigatran, and rivaroxaban significantly lowered the risk of major bleeding (apixaban: HR 0.47, 95%CI 0.35-0.63; dabigatran: HR 0.59, 95%CI 0.47-0.73; rivaroxaban: HR 0.66, 95%CI 0.52-0.83) and lessened the all-cause death rate (apixaban: HR 0.29, 95%CI 0.16-0.52; dabigatran: HR 0.40, 95%CI 0.27-0.60; rivaroxaban: HR 0.42, 95%CI 0.28-0.65). Apixaban (HR 0.59; 95%CI 0.40-0.85) reduced the possibility of ischemic stroke when compared against dabigatran. Rivaroxaban showed a higher chance of causing an ischemic stroke (HR 1.61; 95%CI 1.08-2.41) and major bleeding (HR 1.39; 95%CI 1.02-1.90) than Apixaban. CONCLUSIONS: Apixaban, dabigatran and rivaroxaban were more effective than warfarin on reducing the risks of stroke and haemorrhage; meanwhile, apixaban was likely to lower the risk of major bleeding comparing to rivaroxaban. TRIAL REGISTRATION: PROSPERO registry number: CRD42018086914 .

Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate ameliorates pressure overload-induced cardiac hypertrophy and dysfunction through inhibiting autophagy.

Sodium (±)-5-bromo-2-(a-hydroxypentyl) benzoate (generic name: brozopine, BZP) has been reported to protect against stroke-induced brain injury and was approved for Phase II clinical trials for treatment of stroke-related brain damage by the China Food and Drug Administration (CFDA). However, the role of BZP in cardiac diseases, especially in pressure overload-induced cardiac hypertrophy and heart failure, remains to be investigated. In the present study, angiotensin II stimulation and transverse aortic constriction were employed to induce cardiomyocyte hypertrophy in vitro and in vivo, respectively, prior to the assessment of myocardial cell autophagy. We observed that BZP administration ameliorated cardiomyocyte hypertrophy and excessive autophagic activity. Further results indicated that AMP-activated protein kinase (AMPK)-mediated activation of the mammalian target of rapamycin (mTOR) pathway likely played a role in regulation of autophagy by BZP after Ang II stimulation. The activation of AMPK with metformin reversed the BZP-induced suppression of autophagy. Finally, for the first time, we demonstrated that BZP could protect the heart from pressure overload-induced hypertrophy and dysfunction, and this effect is associated with its inhibition of maladaptive cardiomyocyte autophagy through the AMPK-mTOR signalling pathway. These findings indicated that BZP may serve as a promising compound for treatment of pressure overload-induced cardiac remodelling and heart failure.

IL33 attenuates ventricular remodeling after myocardial infarction through inducing alternatively activated macrophages ethical standards statement.

Interleukin 33 (IL33) has been found to be cardioprotective on various cardiovascular pathologies. However, it is not clear whether IL33 may inhibit myocardial infarction-related ventricular remodeling through inducing macrophage polarization. The objective of present study is to assess whether IL33 can improve ventricular remodeling after myocardial infarction by inducing macrophage polarization. In this study, the direct influence of IL33 on the polarization of macrophages and its mechanism in vitro were investigated. The potential protective effects of IL33 on acute and chronic myocardial infarction (MI) in vivo as well as its underlying mechanism through macrophage polarization were also determined. We found that IL33 significantly enhanced M2 macrophage and decreased the proportion of M1 macrophage. Importantly, IL33 induced M2 macrophage polarization by activating the JAK/STAT signaling pathway. In vivo, IL33 weaken the inflammatory level and myocardial apoptosis after MI and improved the systolic and diastolic function of the heart. Furthermore, IL33 significantly reduced infarct area and prevented the progression of fibrosis by inducing M2 macrophage polarization. The protective effects of IL33 were suppressed by JAK/STAT signaling pathway inhibitor. Our findings highlighted that IL33 not only reduced the early inflammatory response and inhibited myocardial apoptosis, but also increased the number of M2 macrophage in the infarcted area, significantly reduced infarct area and prevented the progression of fibrosis by activating JAK/STAT pathway. Therefore, IL33 may be a novel cardiac protective cytokine for myocardial infarction.

Antibody-Armed Platelets for the Regenerative Targeting of Endogenous Stem Cells.

Stem cell therapies have shown promise in treating acute and chronic ischemic heart disease. However, current therapies are limited by the low retention and poor integration of injected cells in the injured tissue. Taking advantage of the natural infarct-homing ability of platelets, we engineered CD34 antibody-linked platelets (P-CD34) to capture circulating CD34-positive endogenous stem cells and direct them to the injured heart. In vitro, P-CD34 could bind to damaged aortas and capture endogenous stem cells in whole blood. In a mouse model of acute myocardial infarction, P-CD34 accumulated in the injured heart after intravenous administration, leading to a concentration of endogenous CD34 stem cells in the injured heart for effective heart repair. This represents a new technology for endogenous stem cell therapy.