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The coronary artery bypass grafting is a main treatment for restoring the blood supply to the ischemic site by bypassing the narrow part, thereby improving the heart function of the patients. Autologous blood vessels are preferred in coronary artery bypass grafting, but their availability is often limited by due to the underlying disease. Thus, tissue-engineered vascular grafts that are devoid of thrombosis and have mechanical properties comparable to those of natural vessels are urgently required for clinical applications. Most of the commercially available artificial implants are made from polymers, which are prone to thrombosis and restenosis. The biomimetic artificial blood vessel containing vascular tissue cells is the most ideal implant material. Due to its precision control ability, three-dimensional (3D) bioprinting is a promising method to prepare biomimetic system. In the 3D bioprinting process, the bioink is at the core state for building the topological structure and keeping the cell viable. Therefore, in this review, the basic properties and viable materials of the bioink are discussed, and the research of natural polymers in bioink, including decellularized extracellular matrix, hyaluronic acid, and collagen, is emphasized. Besides, the advantages of alginate and Pluronic F127, which are the mainstream sacrificial material during the preparation of artificial vascular graft, are also reviewed. Finally, an overview of the applications in the field of artificial blood vessel is also presented.

Acute myocardial infarction (AMI) remains a dominant origin of morbidity, mortality and disability worldwide. Increases in reactive oxygen species (ROS) are key contributor to excessive cardiac injury after AMI. Here we developed an immobilized enzyme with Superoxide Dismutase (SOD) activity cross-link with Zr-based metal-organic framework (ZrMOF) (SOD-ZrMOF) for mitigate ROS-caused injury. In vitro and in vivo evidence indicates that SOD-ZrMOF exhibits excellent biocompatibility. By efficiently scavenging ROS and suppressing oxidative stress, SOD-ZrMOF can protect the function of mitochondria, reduce cell death and alleviate inflammation. More excitingly, long-term study using an animal model of AMI demonstrated that SOD-ZrMOF can reduce the infarct area, protect cardiac function, promote angiogenesis and inhibit pathological myocardial remodeling. Therefore, SOD-ZrMOF holds great potential as an efficacious and safe nanomaterial treatment for AMI., Graphical abstract Image 1, Highlights • We synthesized a superoxide dismutase immobilized nanocomposite with enhanced stability. • We tested the biocompatibility of SOD-ZrMOF and found it could promote the cell viability and proliferation of H9c2 cells. • SOD-ZrMOF shows excellent performance in protecting mitochondrial function of CMs by eliminating excessive ROS under hypoxia. • SOD-ZrMOF exhibited therapeutic effects on MI heart through inhibiting oxidative stress injury by NF-κB/HIF-1α pathway.

Context A personalized antiplatelet therapy guided by a novel platelet function testing (PFT), PL-12, is considered an optimized treatment strategy in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy may differ in relation to diabetes status. Objective The aim of this study was to compare the outcomes of PFT-guided personalized DAPT in stable CAD patients with and without diabetes mellitus. Methods The PATH-PCI trial randomly assigned 2285 stable CAD patients to either personalized antiplatelet therapy or standard antiplatelet treatment. We investigated the association and interaction of diabetes on clinical outcomes across 2 treatment groups. Results We did not find a significant difference between the personalized group and the standard group in net adverse clinical events in either diabetes patients (10.3% vs 13.4%, P = .224) or in the nondiabetic group (3.1% vs 5.0%, P = .064). In diabetes patients (n = 646, 28.3%), the overall ischemic event rates were significantly low (6.8% vs 11.3%, HR = 0.586, 95% CI, 0.344-0.999, P = .049) and the bleeding event rates did not differ between the 2 groups (3.5% vs 3.3%, HR = 1.066, 95% CI, 0.462-2.458, P = .882). Similarly, in nondiabetic patients, the overall ischemic event rates were significantly low (1.8% vs 4.2%, HR = 0.428, 95% CI, 0.233-0.758, P = .006) and the bleeding event rates did not differ between the 2 groups (1.6% vs 0.9%, HR = 1.802, 95% CI: 0.719-4.516, P = .209). Conclusion The present study suggests that personalized antiplatelet therapy according to PFT can reduce ischemic events but not increase bleedings in stable CAD patients with or without diabetes who have undergone PCI.

Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3‐7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI‐Exo) and healthy controls (Normal‐Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal‐Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT‐PCR of circulating exosomes showed higher expression of miR‐193a‐5p in Normal‐Exo. Our study showed that miR‐193a‐5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR‐193a‐5p, which was confirmed by ACVR1 expression and dual‐luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR‐193a‐5p. While overexpression of ACVR1 could attenuate protective effects of miR‐193a‐5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR‐193a‐5p to protect endothelial cells from oxidative stress damage via ACVR1.

Background: Although numerous studies have suggested that elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) is positively correlated with cardiovascular events, especially the heart failure and heart failure-related death (HFRD), evidence of the association between NT-proBNP and the adverse outcomes of hypertrophic cardiomyopathy (HCM) is still relatively limited. The present study was performed to evaluate the relationship between NT-proBNP and outcomes in patients with HCM. Methods: Observational cohort methodology was used in the present study, and a total of 227 patients were included. And the patients were followed for 44.97 ± 16.37 months. Patients were categorized into three groups according to these NT-proBNP tertiles: first tertile (≤910 pg/ml, n=68), second tertile (913–2141 pg/ml, n=68), and third tertile (≥2151 pg/ml, n=69). The adverse outcomes of the present study were all-cause death (ACD) and cardiac death (CD). Results: According to the risk category of NT-proBNP, the incidence of ACD (P=0.005) and CD (P=0.032) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the ACD and CD in the third tertile have 7.022 folds (hazard risk [HR] = 7.022 [95% confidence interval [CI]: 1.397–35.282], P=0.018) and 7.129 folds (HR = 7.129 [95% CI: 1.329–38.237], P=0.022) increased risks as compared with those in the first tertile. Kaplan–Meier survival analyses showed that the cumulative risks of ACD and CD in patients with HCM tended to increase. Conclusion: The present study indicated NT-proBNP was a novel biomarker suitable for predicting adverse prognosis in patients with HCM, which may be used for early recognition and risk stratification.

IgE-mediated activation of Nhe1 (Na + -H + exchanger-1) induces aortic cell extracellular acidification and promotes cell apoptosis. A pH-sensitive probe pHrodo identified acidic regions at positions of macrophage accumulation, IgE expression, and cell apoptosis in human and mouse abdominal aortic aneurysm (AAA) lesions. Ang II (angiotensin II)–induced AAA in Nhe1-insufficient Apoe −/− Nhe1 +/− mice and Apoe −/− Nhe1 +/+ littermates tested Nhe1 activity in experimental AAA, because Nhe1 −/− mice develop ataxia and epileptic-like seizures and die early. Nhe1 insufficiency reduced AAA incidence and size, lesion macrophage and T-cell accumulation, collagen deposition, elastin fragmentation, cell apoptosis, smooth muscle cell loss, and MMP (matrix metalloproteinase) activity. Nhe1 insufficiency also reduced blood pressure and the plasma apoptosis marker TCTP (translationally controlled tumor protein) but did not affect plasma IgE. While pHrodo localized the acidic regions to macrophage clusters, IgE expression, and cell apoptosis in AAA lesions from Apoe −/− Nhe1 +/+ mice, such acidic areas were much smaller in lesions from Apoe −/− Nhe1 +/− mice. Nhe1-FcεR1 colocalization in macrophages from AAA lesions support a role of IgE-mediated Nhe1 activation. Gelatin zymography, immunoblot, and real-time polymerase chain reaction analyses demonstrated that Nhe1 insufficiency reduced the MMP activity, cysteinyl cathepsin expression, IgE-induced apoptosis, and NF-κB activation in macrophages and blocked IgE-induced adhesion molecule expression in endothelial cells. A near-infrared fluorescent probe (LS662) together with fluorescence reflectance imaging of intact aortas showed reduced acidity in AAA lesions from Nhe-1-insufficient mice. This study revealed extracellular acidity at regions rich in macrophages, IgE expression, and cell apoptosis in human and mouse AAA lesions and established a direct role of Nhe1 in AAA pathogenesis.

OBJECTIVES To determine whether gamma-glutamyl transferase (GGT) to albumin ratio (GAR) independently predicts mortality and bleeding events in coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI). BACKGROUND Serum GGT and albumin levels have been associated with CAD risk and mortality. However, more analysis is needed to determine their predictive relationship with adverse outcomes. METHODS In total, 5,638 patients from a large retrospective cohort study were enrolled from January 2008 to December 2016 and divided into two groups (GAR

Background It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. Methods A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P P = 0.044) and the occurrence of heart failure (log-rank, P P = 0.004) and heart failure (adjusted HR = 1.700 [1.347–2.147], P Conclusions An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.

Background & aims Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance (IR), obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are approved. Ovarian tumor (OTU) domain, ubiquitin aldehyde binding 1 (OTUB1), the founding member of deubiquitinases (DUBs), regulates many metabolism-associated signaling pathways. However, the role of OTUB1 in NASH is unclarified. Methods & results We demonstrated that mice with Otub1 deficiency exhibited aggravated high-fat diet (HFD)- and high-fat high-cholesterol (HFHC) diet-induced hyperinsulinemia and liver steatosis. Notably, hepatocyte-specific overexpression of Otub1 markedly alleviated HFHC diet-induced hepatic steatosis, inflammatory responses and liver fibrosis. Mechanistically, we identified apoptosis signal-regulating kinase 1 (ASK1) as a key candidate target of OTUB1 through RNA-seq analysis and immunoblot analysis. Through immunoprecipitation-mass spectrometry (IP-MS) analysis, we further found that OTUB1 directly bound to tumor necrosis factor receptor-associated factor 6 (TRAF6) and suppressed its lysine 63 (K63)-linked polyubiquitination, thus inhibiting the activation of ASK1 and its downstream pathway. Conclusion OTUB1 is a key suppressor of NASH that inhibits polyubiquitinations of TRAF6 and attenuated TRAF6-mediated ASK1 activation. Targeting the OTUB1-TRAF6-ASK1 axis may be a promising novel therapeutic strategy for NASH.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have well-documented effects on reducing hospitalization for heart failure and cardiovascular mortality, although the effect on atrial fibrillation (AF) has not been comprehensively investigated. Therefore, we performed a meta-analysis to assess the association between SGLT2 inhibitors and AF risk by systematically searching PubMed, Embase, and ClinicalTrials.gov. Two investigators independently identified randomized controlled trials, which compared SGLT2 inhibitors with control in patients with type 2 diabetes, heart failure, or chronic kidney disease. Primary outcomes were incident AF and stroke. We included 20 randomized trials involving 63,604 patients. The SGLT2 inhibitors used were dapagliflozin (7 studies, 28,834 patients), canagliflozin (7 studies, 17,440 patients), empagliflozin (5 studies, 9082 patients), and ertugliflozin (1 study, 8246 patients). Follow-up ranged from 24 weeks to 202 weeks. SGLT2 inhibitors treatment was associated with a significant attenuation in the risk of incident AF (odds ratio = 0.82; 95% confidence interval, 0.72-0.93; P = 0.002) compared with control. No significant difference in stroke between SGLT2 inhibitors and control groups was found (odds ratio = 0.99; 95% confidence interval, 0.85-1.15; P = 0.908). This present meta-analysis indicates that SGLT2 inhibitors are associated with a lower risk of incident AF and do not significantly affect stroke risk for patients with and without type 2 diabetes.

Background: Monocyte count and serum albumin (Alb) have been proven to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI). Methods: We enrolled a total of 3561 patients in the present study from January 2013 to December 2017. They were divided into two groups according to MAR cut-off value (MAR < 0.014, n=2220; MAR ≥ 0.014, n=1119) as evaluated by receiver operating characteristic (ROC) curve. The average follow-up time was 37.59 ± 22.24 months. Results: The two groups differed significantly in the incidences of all-cause mortality (ACM; P Conclusion: The findings of the present study suggested that MAR was a novel independent predictor of long-term mortality in patients who underwent PCI.

Background: Alkaline phosphatase (ALP) and albumin (ALB) have been shown to be associated with coronary artery disease (CAD), and it has been reported that alkaline phosphatase-to-albumin ratio (AAR) is associated with the liver damage and poorer prognosis of patients with digestive system malignancy. Moreover, several previous studies showed that there was a higher incidence of malignancy in CAD patients. However, to our knowledge, the relationship between AAR and long-term adverse outcomes in CAD patients after undergoing percutaneous coronary intervention (PCI) has not been investigated. Therefore, we aim to access the relation between AAR and long-term adverse outcomes in post-PCI patients with CAD. Methods: A total of 3378 post-PCI patients with CAD were enrolled in the retrospective Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-ZZ) study from January 2013 to December 2017. The median duration of follow-up was 37.59 ± 22.24 months. The primary end point was long-term mortality including all-cause mortality (ACM) and cardiac mortality (CM). The secondary end points were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results: Kaplan–Meier analyses showed that an increased AAR was positively correlated with incidences of long-term ACM (log-rank, P=0.014), CM (log-rank, P=0.011), MACEs (log-rank, P=0.013) and MACCEs (log-rank, P=0.006). Multivariate Cox regression analyses showed that the elevated AAR was an independent predictor of long-term ACM (adjusted HR = 1.488 [1.031–2.149], P=0.034), CM (adjusted HR = 1.837 [1.141–2.959], P=0.012), MACEs (adjusted HR = 1.257 [1.018–1.551], P=0.033) and MACCEs (adjusted HR = 1.237 [1.029–1.486], P=0.024). Conclusion: An elevated AAR is a novel independent predictor of long-term adverse outcomes in CAD patients following PCI.

Acute myocardial infarction has a high clinical mortality rate. The initial exclusion or diagnosis is important for the timely treatment of patients with acute myocardial infarction. As a marker, cardiac troponin I (cTnI) has a high specificity, high sensitivity to myocardial injury and a long diagnostic window. Therefore, its diagnostic value is better than previous markers of myocardial injury. In this work, we propose a novel aptamer electrochemical sensor. This sensor consists of silver nanoparticles/MoS2/reduced graphene oxide. The combination of these three materials can provide a synergistic effect for the stable immobilization of aptamer. Our proposed aptamer electrochemical sensor can detect cTnl with high sensitivity. After optimizing the parameters, the sensor can provide linear detection of cTnl in the range of 0.3 pg/ml to 0.2 ng/ml. In addition, the sensor is resistant to multiple interferents including urea, glucose, myoglobin, dopamine and hemoglobin.

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.

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.

Aims/Introduction Diabetes is an important risk factor for atherosclerotic disease. The initiating factor of atherosclerosis is local endothelial cell injury. The arachidonic acid metabolite, 12(S)‐hydroxyeicosatetraenoic acid (12[S]‐HETE), might be involved in this process. In recent years, some studies have discussed the effect of 12(S)‐HETE on vascular endothelial cell function. In the present study, we investigated the effect of 12(S)‐HETE on vascular endothelial cell function in high‐glucose conditions and the mechanisms involved. Materials and Methods Human umbilical vein endothelial cells were cultured in conventional M199 medium and high‐glucose M199 medium. Human umbilical vein endothelial cells were stimulated with 12(S)‐HETE and cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate (a 12/15‐lipoxygenases inhibitor). A type 1 diabetes mellitus model was established in C57BL/6 or 12/15‐lipoxygenases knockout mice with streptozotocin. Aortic tissue was harvested for subsequent testing. The transmembrane transport of dextran and human acute monocytic leukaemia cell line (THP‐1) cells was measured. The adherens junction protein, IkBα, nuclear factor kappa Bp65 (P65), intercellular adhesion molecule 1 and vascular cell adhesion protein 1 expression and phosphorylation, and the binding/dissociation of endothelial cell components were observed. Results Transendothelial migration of dextran and THP‐1 cells was significantly increased by stimulation of human umbilical vein endothelial cell monolayers with high glucose and 12(S)‐HETE (P

We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE−/− mice). Seventy-two apoE−/− mice were fed a western diet and a constrictive silastic tube was used to elicit carotid lesion formation. The animals were separated into a control group, a valsartan group or an LCZ696 group (n = 24 in each group). Plaques in the carotid artery were harvested 12 weeks later for histological examination. The levels of pro-inflammatory genes in the plasma and lesions were detected using real-time PCR and ELISA. Valsartan or LCZ696 treatment remarkably inhibited the expression of pro-inflammatory genes, including interleukin-6, matrix metalloproteinase-8 and monocyte chemotactic protein-1, in comparison with the control group. Meanwhile, both valsartan and LCZ696 suppressed the formation of atherosclerotic plaques by decreasing plaque lipid content and cross-sectional plaque area and increasing the content of plaque collagen and fibrous cap thickness. In particular, LCZ696 performed the best in suppressing atherosclerosis and inhibiting the level of pro-inflammatory genes. LCZ696 significantly ameliorated atherosclerosis and inflammation in apoE−/− mice compared with valsartan.

Background The present study was to assess the prognostic value of fasting blood glucose to high-density lipoprotein cholesterol ratio (GHR) in non-diabetic patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Methods and results A total of 6645 non-diabetic patients from two independent cohorts, the CORFCHD-PCI study (n=4282) and the CORFCHD-ZZ (n=2363) study, were enrolled in Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI. Patients were divided into two groups according to the GHR value. The primary outcome included all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 36.51 ± 22.50 months. We found that there were significant differences between the two groups in the incidences of ACM (P=0.013) and CM (P=0.038). Multivariate Cox regression analysis revealed GHR as an independent prognostic factor for ACM. The incidence of ACM increased 1.284-times in patients in the higher GHR group (hazard ratio [HR]: 1.284 [95% confidence interval [CI]: 1.010–1.631], P Conclusions The present study indicates that GHR index is an independent and novel predictor of ACM in non-diabetic CAD patients who underwent PCI.

Background: Inflammation plays a significant role in the initiation and progression of atherosclerosis. Monocyte and serum albumin have been proved to be involved in the process of systemic inflammation. Therefore, we investigated the prognostic value of monocyte-to-serum albumin ratio (MAR) in patients who underwent percutaneous coronary intervention (PCI).Methods：A total of 3,561 patients enrolled in this study from January 2013 to December 2017, who were divided into two groups according to the cut-off value of MAR (MARResults: There were significant differences between the two groups in the incidences of all-cause mortality (ACM) (PPP=0.038) and major adverse cardiovascular and cerebrovascular events (MACCEs, P=0.037). Kaplan–Meier survival analysis suggested that patients with higher MAR value tended to have an increased accumulated risk of ACM and CM (Log rank PPCI]:1.009–2.115, P=0.045) and CM (HR=1.695, 95% CI:1.056-2.721, P=0.029).Conclusion: The present study suggests that MAR is a novel independent predictor of long-term mortality in patients who underwent PCI.Trial registration: ChiCTR, ChiCTR1800019699. Registered 24 November 2018, http://www.chictr.org.cn/showproj.aspx?proj=33249

Objective In the present study, we aimed to establish a novel score to predict long-term mortality of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI). Methods A total of 2,174 NSTE-ACS patients from the CORFCHD-ZZ study were enrolled as the derivation cohort. The validation cohort including 1,808 NSTE-ACS patients were from the CORFCHD-PCI study. Receiver operating characteristic analysis and area under the curve (AUC) evaluation were used to select the candidate variables. The model performance was validated internally and externally. The primary outcome was cardiac mortality (CM). We also explored the model performance for all-cause mortality (ACM). Results Initially, 28 risk factors were selected and ranked according to their AUC values. Finally, we selected age, N-terminal pro-B-type natriuretic peptide, and creatinine to develop a novel prediction model named “ABC” model. The ABC model had a high discriminatory ability for both CM (C-index: 0.774, p Conclusion In the present study, we developed and validated a novel model to predict mortality in patients with NSTE-ACS who underwent PCI. This model can be used as a credible tool for risk assessment and management of NSTE-ACS after PCI.

Background: The cause of atherosclerosis is not known, and therefore the current treatment options are limited. In the present study, we aimed to investigate the effects of Phoenixin 20 and its receptor G protein-coupled receptor 173 (GPR173) against ox-LDL- induced endothelial dysfunction. Materials and Methods: Human aortic endothelial cells (HAECs) were treated with 10 μg/ml ox-LDL in the presence or absence of phoenixin 20. Gene expression of GPR173, ICAM-1, VCAM-1, IL-1β, IL-8, MCP-1, and NOX-4 were measured by real time PCR. Protein expression was assayed by western blot analysis. Secretions of pro-inflammatory cytokines were measured by ELISA. The attachment of THP-1 monocytes to HAECs was detected using calcein-AM staining. Transcriptional activity of NF-κB was measured using dual-luciferase reporter assay. Results: Our findings indicate that ox-LDL significantly lowered the expression of GPR173 in HAECs and triggered an increase in ROS, NOX-4, and proinflammatory cytokine expression. Importantly, we demonstrate that agonism of GPR173 using phoenixin 20 significantly ameliorated these harmful effects of ox-LDL. We also show that agonism of GPR173 can prevent the attachment of monocytes to endothelial cells, which is an important therapeutic approach to prevent atherogenesis. Conclusion: Here, for the first time to our knowledge, we provide a basis for future research on the role of GPR173 as a new potential treatment against atherosclerosis.

Background: Even though great advances have been made in the treatment of coronary artery disease (CAD) owing to coronary revascularization and modern antiremodeling therapy, it remains the major cause of cardiac morbidity and mortality worldwide. Risk stratification in CAD patients is primarily based on left ventricular ejection fraction (LVEF), risk scores, and some serum markers. The value of baseline Left ventricular fractional shortening (LVFS) level in predicting the clinical outcomes has not yet been determined.Methods: In this retrospective cohort study, a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients without echocardiography data, we finally enrolled 2787 patients. These patients were divided into two groups according to LVFS value. The lower group (LVFS Results: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (PPPPP=0.003), CM (HR: 0.393 [95% CI:0.213-0.725],P=0.003) in acute coronary syndrome (ACS) patients but that it was an independent predictor for only the incidence of CM (HR: 0.153 [95% CI:0.046-0.504],P=0.002) in stable CAD patients.Conclusion This study indicates that baseline LVFS is an independent and novel predictor of adverse long-term outcomes in CAD patients who underwent PCI.Trial registration:Chinese Clinical Trial Registry. ChiCTR-ORC-16010153. Registered 24 November 2018.http://www.chictr.org.cn/index.aspx

The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.

IgE-mediated activation of Na(+)-H(+) exchanger-1 (Nhe1) induces aortic cell extracellular acidification and promotes cell apoptosis. A pH-sensitive probe pHrodo identified acidic regions at positions of macrophage accumulation, IgE expression, and cell apoptosis in human and mouse abdominal aortic aneurysm (AAA) lesions. Angiotensin-II-induced AAA in Nhe1-insufficient Apoe(−/−)Nhe1(+/−) mice and Apoe(−/−)Nhe1(+/+) littermates tested Nhe1 activity in experimental AAA, because Nhe1(–/−) mice develop ataxia and epileptic-like seizures and die early. Nhe1 insufficiency reduced AAA incidence and size, lesion macrophage and T-cell accumulation, collagen deposition, elastin fragmentation, cell apoptosis, smooth muscle cell loss, and matrix metalloproteinase (MMP) activity. Nhe1 insufficiency also reduced blood pressure and the plasma apoptosis marker translationally controlled tumor protein (TCTP), but did not affect plasma IgE. While pHrodo localized the acidic regions to macrophage clusters, IgE expression, and cell apoptosis in AAA lesions from Apoe(−/−)Nhe1(+/+) mice, such acidic areas were much smaller in lesions from Apoe(−/−)Nhe1(+/–) mice. Nhe1-FcεR1 colocalization in macrophages from AAA lesions support a role of IgE-mediated Nhe1 activation. Gelatin zymography, immunoblot, and RT-PCR analyses demonstrated that Nhe1 insufficiency reduced the MMP activity, cysteinyl cathepsin expression, IgE-induced apoptosis, and NF-κB activation in macrophages and blocked IgE-induced adhesion molecule expression in endothelial cells. A near-infrared fluorescent probe (LS662) together with fluorescence reflectance imaging of intact aortas showed reduced acidity in AAA lesions from Nhe-1-insufficient mice. This study revealed extracellular acidity at regions rich in macrophages, IgE expression, and cell apoptosis in human and mouse AAA lesions and established a direct role of Nhe1 in AAA pathogenesis.

The present study aimed to investigate the efficacy and safety of long-term (18 months) dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).A total of 3205 coronary artery disease (CAD) patients after PCI from CORFCHD-PCI, a retrospective cohort study (Identifier: ChiCTR-ORC-16010153), were divided into two groups: monotherapy of aspirin or clopidogrel group (SAPT group, n = 2188 and DAPT group, n = 1017) according to whether to discontinue DAPT 18 months after PCI. After propensity matching analysis (PSM), we included 1017 patients in the DAPT group and 1017 patients in the SAPT group. All the patients were followed-up for at least 18 months and the longest follow-up time is 120 months. The primary endpoint was the incidence of major adverse cardiac events (MACEs). The secondary endpoints were the incidence of major adverse cardiovascular and cerebrovascular events (MACEEs) and bleeding events. We also selected 178 patients for detection of claudin-3 and intestinal fatty acid-binding protein and 58 patients for 16s RNA sequencing of whole blood.The incidences of MACEs (13.9% vs. 9.0%, p = 0.001) and MACCEs (16.3% vs.10.0%, p 0.001) were significantly increased in the DAPT group compared to the SAPT group. We also found DAPT increased the bleeding events compared to SAPT (4.6% vs. 2.9%, p = 0.048). Multivariate Cox regression analyses showed that in the DAPT group, cumulative risk of MACCEs increased 1.797 times (HR = 1.797, 95%CI: 1.429-2.226, p 0.001), MACEs increased 1.737 times (HR = 1.737, 95%CI: 1.360-2.218, p 0.001) and the bleeding events increased 2.129 times (HR = 2.129, 95%CI: 1.388-3.266, p = 0.001) compared to the SAPT group. We also found the plasma concentrations of claudin-3 and intestinal fatty acid-binding protein (I-FABP) were significantly higher in patients in the DAPT group compared with patients in the SAPT group (both p 0.001). Correspondingly, the abundance of blood intestinal bacteria in the DAPT group was significantly increased compared to that in the SAPT group (p 0.001). Furthermore, high-throughput metabolomics analysis suggested that serum level of ceramide (d18:1/16:0) and Neu5Ac was significantly increased in the DAPT group compared to the SAPT group (both p 0.001).The present study suggests that long-term dual antiplatelet therapy longer than 18 months significantly increases the incidence of both ischemic events and bleeding events after PCI. This preliminary study also indicates that long-term DAPT causes intestinal injury, which induces translocation of intestinal bacteria into the bloodstream.

In the present study, we aimed to characterize gut microbiome and develop a gut microbiome-based diagnostic model in patients with coronary artery disease (CAD). Prospectively, we collected 309 fecal samples from Central China and Northwest China and carried out the sequencing of the V3-V4 regions of the 16S rRNA gene. The gut microbiome was characterized, and microbial biomarkers were identified in 152 CAD patients and 105 healthy controls (Xinjiang cohort, n = 257). Using the biomarkers, we constructed a diagnostic model and validated it externally in 34 CAD patients and 18 healthy controls (Zhengzhou cohort, n = 52). Fecal microbial diversity was increased in CAD patients compared to that in healthy controls (P = 0.021). Phylum Bacteroidetes was increased in CAD patients versus healthy controls (P = 0.001). Correspondingly, 48 microbial markers were identified through a 10-fold cross-validation on a random forest model, and an area under the curve (AUC) of 87.7% (95% CI: 0.832 to 0.916, P < 0.001) was achieved in the Xinjiang cohort (development cohort, n = 257). Notably, an AUC of 90.4% (95% CI: 0.848 to 0.928, P < 0.001) was achieved using combined analysis of gut microbial markers and clinical variables. This model provided a robust tool for the prediction of CAD. It could be widely employed to complement the clinical assessment and prevention of CAD.