Triglyceride-glucose index in the prediction of clinical outcomes after successful recanalization for coronary chronic total occlusions.

BACKGROUND: Triglyceride-glucose index (TyG) has been widely used to predict cardiovascular outcomes. However, it remains unclear whether TyG holds prognostic significance for patients with coronary chronic total occlusions (CTO). Thus, our study aimed to evaluate the predictive accuracy and prognostic value of TyG in individuals who underwent successful percutaneous coronary intervention (PCI) for CTO. METHODS: A total of 331 consecutive patients with ≥ 1 successful CTO-PCI were included. The baseline and angiographic data were acquired. The duration of follow-up ranged from 32 to 79 months, with a median of 44 months and an interquartile range of 39 to 67 months. The primary outcome measured was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), including mortality, target vessel revascularization, recurrent myocardial infarction, and stroke. RESULTS: After controlling for confounders, multivariate Cox regression analysis revealed that TyG remained statistically significant, regardless of being a continuous or categorical variable. In the partially adjusted regression model, the Hazard ratio (95%CI) for MACCE was 2.54 (1.12-5.79) in tertile 3 and 1.61 (1.22-2.12) per SD increase in the TyG.Kaplan-Meier survival analysis demonstrated significant differences in MACCE-free survival rates across tertiles of the TyG, as indicated by the log-rank test (p = 0.001). ROC analysis was conducted to evaluate the predictive ability of TyG for MACCE, resulting in an AUC of 0.677. CONCLUSION: The TyG index demonstrates independent predictive capabilities for MACCE in patients who have undergone successful CTO-PCI. These findings suggest that TyG holds the potential as a valuable tool in risk stratification and the identification of patients who may benefit from early intervention in the management of CTO.

The synergy of serum SFRP5 levels and the TyG index in predicting coronary artery disease and prognosing major adverse cardiovascular events.

BACKGROUND AND AIMS: Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that is known for its potent anti-inflammatory properties. Nevertheless, little is known regarding the relevance of SFRP5 in coronary artery disease (CAD). The current study examined the correlation between serum levels of SFRP5 and the triglyceride-glucose (TyG) index in patients who underwent coronary angiography (CAG) as a component of cardiovascular assessment and for the purpose of prognosis evaluation. METHODS: A total of 310 hospitalized patients were enrolled in this study between May 2021 and March 2022 and were divided into three groups based on their CAG results and SYNTAX (synergy between PCI with TAXUS drug-eluting stent and cardiac surgery) scores: the control group, mild lesion group, and moderate-severe lesion group. Univariate and multivariate analyses were employed to investigate the relationships between changes in patients and clinical variables. To investigate the impact of the TyG index and serum SFRP5 levels on the occurrence of major adverse cardiovascular events (MACEs), Kaplan‒Meier curves were plotted. Serum SFRP5 levels were measured utilizing an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The serum SFRP5 levels significantly decreased with the increasing severity and complexity of CAD, while the TyG index significantly increased (P < 0.001). Moreover, a significant negative correlation was observed between the serum SFRP5 levels and the TyG index (r = -0.312, P < 0.001). SFRP5 exerts a protective role in different groups of patients. The area under the receiver operating characteristic (ROC) curve indicated that an SFRP5 concentration > 115.58 pg/mL was the best predictive value for CAD (OR:0.87, P < 0.001). MACEs were significantly associated with serum SFRP5 levels and the TyG index, as indicated by both univariate and multivariate Cox regression analyses (P < 0.001). Furthermore, Kaplan‒Meier analysis indicated that as the TyG index decreased and SFRP5 levels increased, the occurrence of MACEs decreased (P < 0.001). Patients with a concentration of SFRP5 > 115.58 pg/mL and a TyG index < 8.49 exhibited a better prognosis for avoiding MACEs (P < 0.001). CONCLUSION: These results suggest that the collaboration between serum SFRP5 levels and the TyG index holds promise in predicting CAD and its prognosis.

Uric acid to high-density lipoprotein cholesterol ratio predicts adverse cardiovascular events in patients with coronary chronic total occlusion.

BACKGROUND AND AIMS: Uric acid to high-density lipoprotein cholesterol ratio (UHR) is a novel index of metabolism and inflammation proposed by recent studies. The prognostic value of UHR is undetermined in patients with coronary chronic total occlusion (CTO). The aim of this study was to investigate the association of UHR with adverse cardiovascular events in patients with CTO. METHODS AND RESULTS: In this retrospective cohort study, we enrolled 566 patients with CTO lesion in our hospital from January 2016 to December 2019. Patients were divided into three groups based on UHR level. The primary endpoint was major adverse cardiovascular event (MACE), defined as a combination of death, non-fatal MI, target vessel revascularization (TVR), and non-fatal stroke. The median follow-up time of this study was 43 months. During the follow-up, 107 (18.9%) MACEs were recorded. Kaplan-Meier survival plots show the cumulative incidence of MACE-free decreased across tertile of UHR (log-rank test, p < 0.001). In the fully adjusted model, the Hazard ratio (95% CI) of MACE was 2.16 (1.17-3.99) in tertile 3 and 2.01 (1.62-2.49) for per SD increase in UHR. CONCLUSION: Elevated UHR predicts an increasing risk of MACE in patients with CTO. UHR is a simple and reliable indicator for risk stratification and early intervention in CTO patients.

Potential relationship between autophagy and ferroptosis in myocardial ischemia/reperfusion injury.

Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and excessive or dysfunctional organelles. As a pivotal cellular response, autophagy has been extensively studied and is known to be involved in various diseases. Ferroptosis is a recently discovered form of regulated cell death characterized by iron overload, leading to the accumulation of lethal levels of lipid hydroperoxides. Recently, an increasing number of studies have revealed a link between autophagy and ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) is an urgent dilemma after myocardial infarction recanalization, which is regulated by several cell death pathways, including autophagy and ferroptosis. However, the potential relationship between autophagy and ferroptosis in MIRI remains unexplored. In this study, we briefly review the mechanisms of autophagy and ferroptosis, including their roles in MIRI. Moreover, we provide an overview of the potential crosstalk in MIRI. Clarifying the relationship between different cell death pathways may provide new ideas for the treatment of MIRI in the future.

Corrigendum to "Safety and efficacy of ablation index-guided high-power ablation for the treatment of atrial fibrillation" [Heliyon 9 (4), (April 2023) Article e15311].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e15311.].

Sfrp2 regulates the WNT/ß-catenin pathway to slow the development of aldosterone-producing adenoma.

Background: To explore a new drug therapy for aldosterone-producing adenoma (APA), and investigate whether Sfrp2 (secreted frizzled-related protein 2) can influence the development of adrenal APA by regulating the WNT/ß-catenin pathway. Methods: Tissue samples from APA patients were collected to detect the expression of Sfrp2 and ß-catenin in APA. NCI-H295R cells were cultured with WNT/ß-catenin pathway inhibitors to detect cell proliferation and aldosterone secretion. Then, the expression of Sfrp2 was altered to determine the effect of Sfrp2 expression on WNT/ß-catenin pathway activity and aldosterone adenocarcinoma cells. Finally, a mouse APA model was established, and the mice were intravenously injected with WNT/ß-catenin pathway inhibitors or transfected with the Sfrp2 gene. The activity of the WNT/ß-catenin pathway, blood pressure, aldosterone secretion, and cell growth in the mice were then observed. Results: ß-catenin was overexpressed in APA tissues, while Sfrp2 was underexpressed. Sfrp2 can negatively regulate ß-catenin expression and control the activity of the WNT/ß-catenin pathway. Increased Sfrp2 expression inhibited the activity of the WNT/ß-catenin pathway, which suppressed aldosterone secretion and APA cell proliferation. The in vivo experiments also demonstrated that inhibition of WNT/ß-catenin pathway activity in mice reduced the arterial pressure and aldosterone concentration. The increased expression of Sfrp2 can inhibit the WNT/ß-catenin pathway in mice, and can also reduce arterial pressure and APA tissue growth. Conclusions: Sfrp2 can inhibit the WNT/ß-catenin signaling pathway by suppressing the expression of ß-catenin, thus controlling the concentration of aldosterone and hindering APA development. This study provides a novel therapeutic target for the treatment of APA and a new direction for future research.

The interaction between uric acid and high-density lipoprotein cholesterol on the prognosis of patients with acute myocardial infarction.

Background: The significance of uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) in the prognosis of acute myocardial infarction (AMI) remains controversial. This study investigated the effect of the interaction between UA and HDL-C on the prognosis of patients with AMI. Methods: In total, 480 patients with AMI were included in this study. Baseline and follow-up data were collected, and the primary endpoint was major adverse cardiovascular events (MACE). The secondary endpoint was all-cause death. Both additive and multiplicative interactions were calculated to evaluate their interaction with prognosis. Then, the impact of UA and HDL-C ratio (UHR) on prognosis was assessed. Results: Over a median follow-up period of 41 (30,46) months, 136 (28.3%) MACEs, and 44 (9.2%) deaths were recorded. There was a positive additive interaction between UA and HDL-C for MACEs. The attributable proportion (AP) showed that 46% of the estimated effect (MACE in patients) was attributable to this interaction. The synergy index (SI) was 2.04 (1.07,3.88) for MACE, indicating that the risk for patients presenting with both risk factors was greater than the sum of the risk factors alone. Multivariate Cox regression analysis revealed that UHR independently predicted MACEs and mortality. Kaplan-Meier survival curves according to tertiles of UHR showed statistically significant differences in MACE (log-rank test, P < 0.001). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of UHR for predicting MACE was 0.716. Conclusion: The coexistence of high UA and low HDL-C has a synergistic effect and provides further information for risk stratification of patients with AMI. UHR is a simple and easily available prognostic indicator independent of traditional risk factors.

2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

Effect of Levosimendan on B-type Natriuretic Peptide Levels in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to evaluate the effects of levosimendan on B-type natriuretic peptide (BNP) levels in patients with decompensated heart failure and assess the efficacy and safety of levosimendan in treating left heart failure. Methods: Randomized controlled trials (RCTs) were identified through searches in the Chinese Biomedical Literature Database (CBM), Chinese Academic Journal Full Text Database (CNKI), Wanfang Database (CECDB), VIP Chinese Scientific, PubMed, Cochrane Library, and Web of Science. Quality assessment and data extraction were performed for the included studies, and meta-analysis was conducted using Review Manager 5.2 software. Results: The meta-analysis revealed a statistically significant difference in the regulatory effect of levosimendan on BNP levels in patients with stage III heart failure compared to the control group [OR = 2.12, 95% CI (1.22, 3.67), P = .008, I2 = 37%, Z = 2.67]. Additionally, leosimendan showed a significant effect on BNP levels in patients with stage IV heart failure [OR = 1.88, 95% CI (1.27, 2.79), P = .002, I2 = 0%, Z = 3.14], compensatory heart failure [OR=2.97, 95% CI (1.81, 4.86), P < .0001, I2 = 55%, Z = 4.32], and decompensated heart failure [OR = 1.98, 95% CI (1.59, 2.47), P < .00001, I2 = 76%, Z = 6.07]. Conclusions: Levosimendan administration demonstrated improved cardiac function and a significant reduction in plasma BNP levels in patients with decompensated heart failure.

Acetylation, ferroptosis, and their potential relationships: Implications in myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a serious complication affecting the prognosis of patients with myocardial infarction and can cause cardiac arrest, reperfusion arrhythmias, no-reflow, and irreversible myocardial cell death. Ferroptosis, an iron-dependent, peroxide-driven, non-apoptotic form of regulated cell death, plays a vital role in reperfusion injury. Acetylation, an important post-translational modification, participates in many cellular signaling pathways and diseases, and plays a pivotal role in ferroptosis. Elucidating the role of acetylation in ferroptosis may therefore provide new insights for the treatment of MIRI. Here, we summarized the recently discovered knowledge about acetylation and ferroptosis in MIRI. Finally, we focused on the acetylation modification during ferroptosis and its potential relationship with MIRI.

Lipoprotein (a) and myocardial infarction: impact on long-term mortality.

BACKGROUND AND AIMS: Lipoprotein (a) [Lp(a)] is a genetically regulated lipoprotein particle that is an independent risk factor for coronary atherosclerotic heart disease. However, the correlation between Lp(a) and left ventricular ejection fraction (LVEF) in patients with myocardial infarction (MI) has been poorly studied. The present study investigated the correlation between Lp(a) and LVEF, as well as the impact of Lp(a) on long-term mortality in patients with MI. METHODS: Patients who underwent coronary angiography resulting in MI diagnosis between May 2018 and March 2020 at the First Affiliated Hospital of Anhui Medical University were included in this study. The patients were divided into groups based on the Lp(a) concentration and LVEF (reduced ejection fraction group: < 50%; normal ejection fraction group: ≥ 50%). Then, correlations between the Lp(a) level and LVEF, as well as the impact of Lp(a) on mortality, were assessed. RESULTS: This study included 436 patients with MI. The Lp(a) level and LVEF were significantly and negatively correlated (r = -0.407, ß = -0.349, P < 0.001). The area under the receiver operating characteristic curve (ROC) indicated that an Lp(a) concentration > 455 mg/L was the best predictive value for reduced ejection fraction (AUC: 0.7694, P < 0.0001). The clinical endpoints did not differ based on the Lp(a) concentration. However, all-cause mortality and cardiac mortality differed based on LVEF. CONCLUSIONS: These results suggest that an elevated Lp(a) concentration predicts reduced ejection fraction and that LVEF predicts all-cause mortality and cardiac mortality in patients with MI.

The diagnostic performance of AccuFFRangio for evaluating coronary artery stenosis under different computational conditions.

Background: A computational method (AccuFFrangio) based on invasive coronary angiography (ICA) and computational fluid dynamics (CFD) to calculate fractional flow reserve (FFR) without a pressure wire has been devised to clarify the physiological significance of coronary stenosis. This study aimed to evaluate the diagnostic performance of AccuFFRangio computation under different boundary conditions and vessel reconstruction approaches. Methods: Consecutive patients with stable angina pectoris who underwent ICA and FFR assessment from 2 centers were analyzed retrospectively. Using wire-based FFR as the reference standard, the diagnostic performances of AccuFFRangio and its variations were evaluated and compared. The calculation of AccuFFRangio involves several key boundary conditions, including patient-specific aortic pressure, contrast flow velocity derived from the thrombolysis in myocardial infarction (TIMI) frame count method, and vessel reconstruction based on 2 angiographic views. We considered the following 3 variations: (I) a fixed aortic pressure [fixed pressure AccuFFRangio (pAccuFFRangio)], (II) an empirical hyperemic velocity [fixed velocity AccuFFRangio (vAccuFFRangio)], and (III) vessel reconstruction using a single angiographic view [single view AccuFFRangio (sAccuFFRangio)]. Results: A total of 230 patients with 230 vessels were included in the final analysis. The accuracy for standard AccuFFRangio, pAccuFFRangio, vAccuFFRangio, and sAccuFFRangio was 93.91%, 86.52%, 81.74%, and 83.48%, respectively; the sensitivity was 90.74%, 51.85%, 83.33%, and 46.30%, respectively; the specificity was 94.89%, 97.16%, 81.25%, and 94.89%, respectively; and the area under the receiver operating characteristic curve was 0.971, 0.928, 0.892, and 0.870, respectively. Conclusions: The comparison suggested that the overall performance of the standard AccuFFRangio was superior to other variations and had the highest accuracy among all the cases.

Anticoagulation therapy and clinical outcomes following transcatheter mitral valve repair for patients with mitral regurgitation: A meta-analysis.

Transcatheter mitral valve repair (TMVR) using MitraClip (MC) is now an established technique in the interventional treatment of mitral regurgitation. Common complications after MC procedure are bleeding and ischemic events. However, 2017 ESC/EACTS and 2020 ACC/AHA did not give a clear antithrombotic protocol, the policy has been based on clinical experience. Here, we performed a meta-analysis comparing outcomes with and without the addition of anticoagulants after TMVR. We searched the Cochrane Library, EMBASE, PubMed, and Web of Science from inception to October 6, 2022 to identify studies with or without the use of anticoagulants after TMVR. From each study, we extracted the number of people with bleeding, stroke, combined endpoints, and all-cause death. Five observational cohort studies were included, enrolling a total of 1892 patients undergoing TMVR who were assigned to either the anticoagulation group (n = 1209) or the no-anticoagulation group (n = 683). Pooled analysis showed a significantly lower stroke rate in the anticoagulated group (at least 4 weeks duration) compared with the non-anticoagulated group (RR [95% CI] = 0.14 [0.0-0.77], p = 0.02), and similar rates of bleeding, combined endpoints, and all-cause death in both groups (RR [95% CI] = 0.76 [0.48-1.22], p = 0.26), (RR [95% CI] = 0.52 [0.10-2.63], p = 0.43), and (RR [95% CI] = 0.89 [0.58-1.35], p = 0.58). We observed a reduced risk of stroke without elevated risk of bleeding, combined endpoints, or all-cause death in patients using anticoagulants (at least 4 weeks duration) after TMVR compared to no anticoagulants.

Safety and efficacy of ablation index-guided high-power ablation for the treatment of atrial fibrillation.

Objective: To study the safety and efficacy of high-power ablation for atrial fibrillation (AF) guided by lesion size index (LSI) and impedance cutoff. Method: A total of 223 patients who underwent radiofrequency catheter ablation of atrial fibrillation (including paroxyparal atrial fibrillation and persistent atrial fibrillation) in the Department of Cardiology of Anhui Provincial Hospital from February 2019 to July 2020 were enrolled, and were divided into 123 patients in the high-power ablation group (HPAI) and 100 patients in the conventional power ablation group (CPAI). The HPAI group adopted high-power (40-50 W) ablation by impedance cutoff, and the CPAI group adopted conventional-power (30-35 W) ablation. Patients in both groups were ablated guided by the same LSI. For both groups, we analyzed the pulmonary vein single-circle isolation rate, ablation time, X-ray exposure, impedance drop value, incidence of complications, and recurrence rate within one year after operation. Results: There was no significant difference in the success rate of pulmonary vein single-circle isolation, X-ray perspective time, and X-ray exposure quantity between the HPAI group and the CPAI group (88.60% vs 82.00%, P = 0.161; 8.7 ± 3.74 min vs 7.82 ± 3.86 min, P = 0.067; 54.74 ± 28 min vs 52.78 ± 39.58 min, P = 0.139); the annular pulmonary vein ablation time and total ablation time were less in the HPAI group (35.74 ± 7.25 min vs 65.49 ± 7.34 min, P < 0.01; 55.42 ± 11.61 min vs 76.9 ± 6.79 min, P < 0.01); the impedance drop values at 10-15Ω and 15-20Ω were higher in the HPAI group (25.3% vs 19.1%, P < 0.05; 24.1% vs 19.1%, P < 0.05); there was no significant difference in the recurrence rate within one year after operation between the two groups; and no serious complications occurred in the two groups. Conclusion: High-power ablation guided by LSI and impedance cutoff could significantly shorten the AF ablation time and reduce complications.

LncRNA HOXA11-AS promotes vascular endothelial cell injury in atherosclerosis by regulating the miR-515-5p/ROCK1 axis.

AIMS: Long non-coding RNA HOXA11-AS participated in heart disease. In this study, we aim to evaluate the potential roles of HOXA11-AS in atherosclerosis and its underlying mechanisms. METHODS AND RESULTS: The expression levels of HOXA11-AS in ox-LDL-treated HUVECs and arch tissues of high-fat diet-fed ApoE-/- mice (n = 10) were assessed by qRT-PCR. The effects of HOXA11-AS knockdown on the development of atherosclerosis were evaluated using in vitro and in vivo models. Luciferase reporter and RNA immunoprecipitation (RIP) assays verified the potential relationships between HOXA11-AS or ROCK1 and miR-515-5p. The interactive roles between HOXA11-AS and miR-515-5p and between miR-515-5p and ROCK1 were further characterized in ox-LDL-treated HUVECs. Our data showed that HOXA11-AS was significantly up-regulated (P < 0.001), whereas miR-515-5p was dramatically down-regulated in AS mice tissues (P < 0.001) and ox-LDL-treated HUVECs (P < 0.01). Ox-LDL could induce endothelial injuries by inhibiting cell proliferation (P < 0.001) and SOD synthesis (P < 0.001), promoting apoptosis (P < 0.01), ROS (P < 0.001), and MDA production (P < 0.001), increasing Bax (P < 0.001) and cleaved Caspase-3 (P < 0.001), and decreasing Bcl-2 (P < 0.001) and phosphorylated eNOS (P < 0.01). HOXA11-AS knockdown attenuated endothelial injuries via increasing eNOS phosphorylation. Luciferase assay and RIP results confirmed that miR-515-5p is directly bound to HOXA11-AS and ROCK1. HOXA11-AS promoted ox-LDL-induced HUVECs injury by directly inhibiting miR-515-5p from increasing ROCK1 expression and subsequently decreasing the expression and phosphorylation of eNOS. MiR-515-5p mimics could partially reverse the effects of HOXA11-AS knockdown. CONCLUSIONS: HOXA11-AS contributed to atherosclerotic injuries by directly regulating the miR-515-5p/ROCK1 axis. This study provided new evidence that HOXA11-AS might be a candidate for atherosclerosis therapy.

Risk Prediction of Coronary Artery Stenosis in Patients with Coronary Heart Disease Based on Logistic Regression and Artificial Neural Network.

Objective: Coronary heart disease (CHD) is considered an inflammatory relative disease. This study is aimed at analyzing the health information of serum interferon in CHD based on logistic regression and artificial neural network (ANN) model. Method: A total of 155 CHD patients diagnosed by coronary angiography in our department from January 2017 to March 2020 were included. All patients were randomly divided into a training set (n = 108) and a test set (n = 47). Logistic regression and ANN models were constructed using the training set data. The predictive factors of coronary artery stenosis were screened, and the predictive effect of the model was evaluated by using the test set data. All the health information of participants was collected. Expressions of serum IFN-γ, MIG, and IP-10 were detected by double antibody sandwich ELISA. Spearman linear correlation analysis determined the relationship between the interferon and degree of stenosis. The logistic regression model was used to evaluate independent risk factors of CHD. Result: The Spearman correlation analysis showed that the degree of stenosis was positively correlated with serum IFN-γ, MIG, and IP-10 levels. The logistic regression analysis and ANN model showed that the MIG and IP-10 were independent predictors of Gensini score: MIG (95% CI: 0.876~0.934, P < 0.001) and IP-10 (95% CI: 1.009~1.039, P < 0.001). There was no statistically significant difference between the logistic regression and the ANN model (P > 0.05). Conclusion: The logistic regression model and ANN model have similar predictive performance for coronary artery stenosis risk factors in patients with CHD. In patients with CHD, the expression levels of IFN-γ, IP-10, and MIG are positively correlated with the degree of stenosis. The IP-10 and MIG are independent risk factors for coronary artery stenosis.

LncRNA LINC00461 exacerbates myocardial ischemia-reperfusion injury via microRNA-185-3p/Myd88.

OBJECTIVE: Long non-coding RNAs (lncRNAs) play critically in the pathogenesis of myocardial ischemia-reperfusion (I/R) injury. Thus, it was proposed to investigate the mechanism of LINC00461 in the disease through mediating microRNA-185-3p (miR-185-3p)/myeloid differentiation primary response gene 88 (Myd88) axis. METHODS: miR-185-3p, LINC00461 and Myd88 expression in mice with I/R injury was measured. Mice with I/R injury were injected with the gene expression-modified vectors, after which cardiac function, hemodynamics, myocardial enzyme, oxidative stress, and cardiomyocyte apoptosis were analyzed. RESULTS: I/R mice showed LINC00461 and Myd88 up-regulation and miR-185-3p down-regulation. Down-regulating LINC00461 or up-regulating miR-185-3p recovered cardiac function, reduced myocardial enzyme levels, and attenuated oxidative stress and cardiomyocyte apoptosis in mice with I/R. miR-185-3p overexpression rescued the promoting effect of LINC00461 upregulation on myocardial injury in I/R mice. CONCLUSION: LINC00461 knockdown attenuates myocardial I/R injury via elevating miR-185-3p expression to suppress Myd88 expression.

Inhibition of MicroRNA-92 alleviates atherogenesis by regulation of macrophage polarization through targeting KLF4.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease in which macrophage polarization plays an important role in contribution to atherosclerotic plaque formation and stability. Here we tested the effect of miR-92 regulation on the development of atherosclerosis beyond tumorigenesis and explored the potential mechanism. METHODS AND RESULTS: In the present study, bone marrow derived macrophages (BMDMs), mouse peritoneal macrophages (MPMs), and human macrophages were used to test the expression of miR-92. Here we noticed miR-92 levels were enhanced in classic M1 macrophage but decreased in alternative M2 macrophage, respectively. In vitro, we demonstrated that macrophages transfected with miR-92 inhibitor attenuated proinflammatory cytokine secretion represented by polarized M1 markers but promoted anti-inflammatory state that was indicative of an M2 phenotype. Mechanistically, miR-92 was found to directly interact with KLF4 and we further identified a requirement role of KLF4 in mediating the effect of miR-92 silencing macrophage polarization. Concomitantly, miR-92 inhibition treated ApoE-/- mice promoted macrophage polarization toward alternative M2 macrophage, thus protecting against atherosclerotic plaque formation and preventing a vulnerable phenotype. CONCLUSION: miR-92 inhibition promoted alternative macrophage activation and attenuated atherosclerosis regression partially regulated in a KLF4-dependent manner, which indicated that miR-92/KLF4 axis may serve as a promising strategy for prevention of atherosclerotic diseases.

Cholecystokinin-mediated pharmacological preconditioning effects on ischemic rat hearts: Possible signaling pathways.

BACKGROUND: Cholecystokinin (CCK-8) has been shown to exhibit pharmacological preconditioning and cardioprotective effects. However, the molecular mechanisms involved in CCK-8-induced pharmacological preconditioning have not yet been clarified. OBJECTIVES: The current study explored the molecular mechanisms involved in CCK-8-mediated pharmacological preconditioning effects on ischemic rat hearts. MATERIAL AND METHODS: Pharmacological preconditioning was induced in male Wistar rats by administration of CCK-8 (20 µg/kg) 24 h before heart isolation. The PI3K inhibitor LY294002 (10 mg/kg and 20 mg/kg) and the HIF-1α inhibitor YC-1 (1 mg/kg and 2 mg/kg) were administered 30 min before the administration of CCK-8. The hearts were subjected to ischemia-reperfusion (IR) injury using a Langendorff apparatus. Myocardial injury was quantified by measuring the release of LDH-1, CK-MB and cTnT. The levels of HIF-1α and p-Akt expression and the ratio of p-GSK-3ß/GSK-3ß, were assessed in the heart homogenates. RESULTS: Pharmacological preconditioning with CCK-8 reduced IR-induced increases in the release of LDH, CK-MB and cTnT. Moreover, it restored the expression of HIF-1α and p-Akt, and the p-GSK-3ß/GSK-3ß ratio. However, administration of LY294002 or YC-1 with CCK-8 significantly abolished the cardioprotective effects of pharmacological preconditioning. The PI3K and HIF-1α inhibitors also abolished the effects of CCK-8 preconditioning on HIF-1α, p-Akt and p-GSK-3ß/GSK-3ß. CONCLUSIONS: Based on these findings, it may be concluded that the molecular mechanisms participating in CCK-8-induced pharmacological preconditioning involve HIF-1α, PI3K, Akt, and GSK-3ß signaling pathways.

Trajectories of Waist-to-Hip Ratio and Adverse Outcomes in Heart Failure with Mid-Range Ejection Fraction.

BACKGROUND: Waist-to-hip ratio (WHR) is a strong predictor of mortality in patients with heart failure (HF). However, common WHR trajectories are not well established in HF with mid-range ejection fraction (HFmrEF) persons, and their relationship to clinical outcomes remains uncertain. METHOD: We prospectively enrolled 1,396 participants with HFmrEF (left ventricular ejection fraction 40-49%) from April 2013 through April 2017. The waist and hip circumferences of the subjects were measured at regular intervals, and the WHR was calculated as waist circumference divided by hip circumference. Latent mixture modeling was performed to identify WHR trajectories. We then used Cox proportional-hazard models to examine the association between WHR trajectory patterns and incident HF, incident cardiovascular disease (CVD), and all-cause mortality. RESULTS: We identified four distinct WHR trajectory patterns: lean-moderate increase (9.2%), medium-stable/increase (32.7%), heavy-stable/increase (48.0%), and heavy-moderate decrease (10.1%). After multivariable adjustment, the heavy-stable/increase and heavy-moderate decrease patterns were associated with an increased all-cause mortality risk (heavy-stable/increase: adjusted hazard ratio [HR] 3.18, 95% confidence interval [CI] 2.75-4.62; heavy-moderate decrease: adjusted HR 2.32, 95% CI 1.71-3.04), incident CVD risk (heavy-stable/increase: adjusted HR 4.03, 95% CI 2.39-4.91; heavy-moderate decrease: adjusted HR 3.05, 95% CI 2.34-4.09), and incident HF risk (heavy-stable/increase: adjusted HR 2.72, 95% CI 2.05-3.28; heavy-moderate decrease: adjusted HR 2.39, 95% CI 1.80-3.03) with reference to the lean-moderate increase pattern. CONCLUSION: Among patients with HFmrEF, the trajectories of WHR gain are associated with poor outcomes. These findings highlight the importance of abdominal fat accumulation management during the progression of HFmrEF.