Impact of anemia on in-stent restenosis after percutaneous coronary intervention.

BACKGROUND: Anemia is a common risk factor for post-percutaneous coronary intervention (PCI) adverse events; however, data on its association with in-stent restenosis (ISR) is limited. METHODS: 538 patients who underwent PCI between January 2017 and September 2019 and follow-up angiography 9-12 months after the initial PCI were enrolled in this study. Baseline clinical and procedural characteristics were compared between the ISR and non-ISR groups, and independent predictors of ISR were determined using propensity score matching. RESULTS: The incidence of anemia was 53.5% in patients with ISR and 19.0% in those without ISR. Univariable logistic regression analyses showed that anemia (OR, 4.283; 95% CI, 1.949-9.410; P < 0.001), diabetes mellitus (OR, 2.588; 95% CI, 1.176-5.696; P = 0.018), chronic kidney disease (OR, 3.058; 95% CI, 1.289-7.252; P = 0.011), multiple stenting (OR, 2.592; 95% CI, 1.205-5.573; P = 0.015), bifurcation lesion (OR, 2.669; 95% CI, 1.236-5.763; P = 0.012), and calcification (OR, 3.529; 95% CI, 1.131-11.014; P = 0.030) were closely associated with ISR. Low-density lipoprotein cholesterol (LDL-c) levels and stent diameter were also significantly linked to ISR, as was anemia (P = 0.009) after propensity score matching. CONCLUSION: Anemia is closely associated with post-PCI ISR, and patients with lower hemoglobin levels are at a higher risk of ISR.

Knockdown of circ_0060745 alleviates acute myocardial infarction by suppressing NF-κB activation.

It has been shown that circRNAs are involved in the development of heart diseases. However, few studies explored the role of circRNAs in acute myocardial infarction (AMI). The present study aims to investigate the role of circ_0060745 in the pathogenesis of AMI. We found that the expression of circ_0060745 was significantly increased in the myocardium of AMI mice and was mainly expressed in myocardial fibroblasts. The knockdown of circ_0060745 decreased myocardial infarct size and improved systolic cardiac functions after AMI. The knockdown of circ_0060745 in cardiac fibroblasts inhibited the migration of peritoneal macrophage, the apoptosis of cardiomyocytes and the expressions of IL-6, IL-12, IL-1ß, TNF-α and NF-κB under hypoxia. Overexpression of circ_0060745 caused an increase in infarct size and worsened cardiac functions after AMI. In summary, our findings showed that knockdown of circ_0060745 mitigates AMI by suppressing cardiomyocyte apoptosis and inflammation. These protective effects could be attributed to inhibition of NF-κB activation.

Relationship between fluoroquinolones and the risk of aortic diseases: a meta-analysis of observational studies.

BACKGROUND: Our aim was to determine the relationship between the use of fluoroquinolones and the risk of aortic diseases. METHODS: PubMed, EMBASE and the Web of Science were searched from inception to July 6, 2019, to identify observational studies that evaluated the risk of aortic diseases associated in users of fluoroquinolones compared with nonusers or users of other antibiotics. The primary outcome was the first occurrence of aortic diseases. We used the GRADE approach to rate the strength of evidence. We used the inverse variance method random-effect model to estimate the odds ratios (ORs) with 95% CIs, and statistical heterogeneity was assessed by the I2 statistic. RESULTS: This meta-analysis enrolled 2,829,385 patients reported the relationship between fluoroquinolones and the risk of aortic diseases. Compared with nonusers or users of other antibiotics, users of fluoroquinolone had a significantly increased risk of aortic diseases (adjusted OR, 2.10; 95% CI, 1.65-2.68; P = .000, I2 = 16.4%). The quality of evidence was moderate, and the number needed to harm (NNH) for aortic diseases among patients was estimated to be 1301. CONCLUSIONS: The fluoroquinolone use in patients significantly increases the risk of new-onset aortic diseases. Clinicians need to pay attention to these severe adverse events when considering fluoroquinolone use.

MicroRNA-98 attenuates cardiac ischemia-reperfusion injury through inhibiting DAPK1 expression.

Cardiovascular ischemic disease is a large class of diseases that are harmful to human health. The significant role of microRNAs (miRNAs) in terms of controlling cardiac injury has been reported in latest studies. MiR-98 is very important in regulating the apoptosis, the differentiation, the growth as well as the metastasis of cells. Nevertheless, the effect of miR-98 in the cardiac ischemia reperfusion (I/R) injury has rarely been investigated. In the current research, we found that the miR-98 expression was down-regulated in the cardiomyocytes subjected to hypoxia/reoxygenation (H/R) and in the myocardium of the I/R rats. In addition, over-expression of miR-98 could significantly reduce the myocardial oxidative stress and ischemic injury as well as cell apoptosis. In agreement, similar findings were demonstrated in H9c2 cells subjected to H/R injury. Bioinformatic analysis using MiRanda and TargetScan and luciferase activity assay confirmed death-associated protein kinase 1 (DAPK1) as a direct target of miR-98. These findings suggest that miR-98 may be exploited as a novel molecular marker or therapeutic target for myocardial I/R injury. © 2018 IUBMB Life, 71(1):166-176, 2019.

WITHDRAWN: Resveratrol increases microRNA-130a expression to promote angiogenesis and improve heart functions in mice after myocardial infarction.

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Permanent pacemaker implanted into patient's left ventricle via subclavian artery by mistake: a case report.

BACKGROUND: Although various iatrogenic complications could be observed in the process of permanent pacemaker implantation, pacemaker electrode mistakenly implanted into left ventricle via subclavian artery and aortic valve has not been reported. CASE PRESENTATION: Herein, we reported a 71-year-old woman with permanent pacemaker mistakenly implanted into the left ventricle. During the operation of permanent pacemaker implantation, puncture was performed on her subclavian artery by mistake, and then the pacemaker electrode was put into the cardiac apex of left ventricle via ascending aorta reversely. CONCLUSION: The further operation could be conducted.

Protective effects of tanshinone IIA on myocardial ischemia reperfusion injury by reducing oxidative stress, HMGB1 expression, and inflammatory reaction.

CONTEXT: Although there were reports on the protective functions of tanshinone IIA (TSA) on rat myocardial ischemia, the exerting mechanism has not been completely clarified. OBJECTIVE: An attempt was made to further verify the protective effect of TSA on myocardial ischemia reperfusion injury and elucidate its underlying mechanism. MATERIALS AND METHODS: The rats were given TSA (10, 20, and 40 mg/kg bw per day) in intraperitoneal injection for 15 d. Rami anterior descending branch of coronary artery was ligated for 30 min and then re-perfused for 120 min to establish a reperfusion model. Effects of TSA on the infarct area, creatine kinase (CK), aspartate aminotransferase (AST), high mobility group box B1 protein (HMGB1), and inflammation and oxidation were investigated. RESULTS: Compared with those in the IR group, infarct size percentages of rats' myocardium in L-TSA, M-TSA, and H-TSA groups were reduced by 1.21, 4.26, and 12.50%, respectively, CK activities by 7.4, 11.2, and 12.5%, respectively, and AST activities also declined (p < 0.05). Furthermore, compared with those in the IR group, SOD and GSH-Px activities increased, and MDA, TNF-α, IL-6, and iNOS levels decreased in L-TSA, M-TSA, and H-TSA groups (p < 0.05). Meanwhile, compared with those in the IR group, HMGB1 expressions in L-TSA, M-TSA, and H-TSA groups were lowered by 21.9, 32.4, and 35.6%, respectively. DISCUSSION AND CONCLUSION: The protective function of TSA on myocardial ischemia reperfusion injury may be possibly exerted by inhibiting the increase of ROS caused by the reperfusion to attenuate the expression of HMGB1 and inhibit inflammation.

Sleep Quality, Sleep Duration, and the Risk of Adverse Clinical Outcomes in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with varying underlying etiologies and occurs in ~5-10% of patients with acute myocardial infarction. Sleep disorders and short sleep duration are common phenomena experienced by patients with coronary heart disease and are associated with poor clinical outcomes. However, the association between sleep quality, sleep duration, and the MINOCA prognosis is less clear. Methods: We performed a prospective observational study of 607 patients with MINOCA between February 2016 and June 2018. The mean follow-up period was 3.9 years. Sleep quality and sleep duration were measured by the Chinese version of the Pittsburgh Sleep Quality Index. The primary endpoint was all-cause mortality, and the secondary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, stroke and heart failure hospitalization. Results: During the follow-up period, all-cause death occurred in 69 participants and 105 participants developed MACE. The Kaplan-Meier survival analysis demonstrated a significant association between poor sleep quality and all-cause mortality (log-rank P = 0.005) and MACE (log-rank P = 0.004). Multivariable Cox regression model indicated that poor sleep quality was an independent predictor of all-cause mortality as well as MACE [adjusted hazard ratio (HR) = 1.649; 95% confidence interval (CI), 1.124-2.790; P < 0.001; and adjusted HR = 1.432; 95% CI, 1.043-2.004; P = 0.003, respectively]. For sleep duration, short sleep duration (<6 h/d) was significantly associated with an increased risk of all-cause mortality and MACE (adjusted HR = 1.326; 95% CI, 1.103-1.812; P = 0.004; and adjusted HR = 1.443; 95% CI, 1.145-1.877; P < 0.001, respectively), whereas long sleep duration was not (>8 h/d). A poorer sleep profile (including poor sleep quality and short sleep duration) was associated with a 149.4% increased risk of death (HR = 2.494; 95% CI, 1.754-4.562; P < 0.001) and a 96.7% increased risk of MACE (HR = 1.967; 95% CI, 1.442-3.639; P < 0.001) than those with neither. Conclusion: Sleep disorders were common among Chinese patients with MINOCA. Poor sleep quality and short sleep duration were independently associated with an increased risk of all-cause mortality and MACE in the MINOCA population. Meanwhile, a poor sleep profile has an additive effect with regard to cardiovascular risks; in these populations, efforts should be made to improve both sleep quality and sleep duration for secondary cardiovascular prevention. Clinical Trial Registration: http://www.chictr.org.cn, identifier: ChiCTR2000040701.

Ferroptosis: A Novel Therapeutic Target for Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury is a major cause of cell death and organ damage in numerous pathologies, including myocardial infarction, stroke, and acute kidney injury. Current treatment methods for I/R injury are limited. Ferroptosis, which is a newly uncovered type of regulated cell death characterized by iron overload and lipid peroxidation accumulation, has been investigated in various diseases. There is increasing evidence of a close association between ferroptosis and I/R injury, with ferroptosis frequently identified as a new therapeutic target for the management of I/R injury. This review summarizes the current status of ferroptosis and discusses its relationship with I/R injury, as well as potential treatment strategies targeting it.

MicroRNA-101a protects against the H2O2-induced injury on cardiomyocytes via targeting BCL2L11.

OBJECTIVE: MicroRNAs (miRs) have been confirmed to be involved in the development of cardiovascular diseases, in spite of numerous studies elucidating the effect and mechanism of miRs in the progression of cardiac ischemia reperfusion injury (I/R), the understanding of their roles is still limited. METHODS: All rats underwent the same I/R procedure, while sham group experienced the surgical procedure but without the ligation of left anterior descending coronary artery (LAD). RESULTS: Here, we found miR-101a which was proved down-regulated significantly in myocardium and cariomyocytes subjected to I/R and H2O2 treatment respectively. In vivo and in vitro studies determined the protective role of miR-101a from I/R and oxidative stress injury. It attenuated the size of ischemia area and the cardiomycyte apoptosis under I/R and H2O2 treatment. Mechanically, BCL2L11 was predicted and then verified to be targeted by miR-101a. Moreover, rescue experiment and RNA pull down further verified the interaction between miR-101a and BCL2L11. CONCLUSIONS: Our findings revealed miR-101a may be a therapeutic target for the therapeutic target for ischemic heart diseases and expanded our understanding of the molecular mechanism underling the progression of I/R injury.

Long non-coding RNA NEAT1 modulates hypoxia/reoxygenation-induced cardiomyocyte injury via targeting microRNA-520a.

In the present study, a hypoxia/reoxygenation (H/R) model of cardiomyocytes was established to investigate the effects of long non-coding RNA (LncRNA) Nuclear Enriched Abundant Transcript 1 (NEAT1) and microRNA (miR)-520a on H/R-induced cardiomyocyte apoptosis. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling staining were used to evaluate cell apoptosis. Luciferase activity assay was used to investigate whether miR-520a targets NEAT1. Results revealed that NEAT1 was significantly upregulated and miR-520a was downregulated in the ischemia/reperfusion myocardium and the cardiomyocytes that received H/R treatment. Further study demonstrated that knockdown of NEAT1 and overexpression of miR-520a serves a protective role against H/R-induced cardiomyocyte apoptosis. miR-520a directly targets NEAT1 and its expression level is negatively correlated with that of NEAT1. The findings suggested that NEAT1 and miR-520a may protect cardiomyocytes from apoptosis through regulating apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein, and altering cleaved caspase3 expression levels.

miR-190 protects cardiomyocytes from apoptosis induced by H2O2 through targeting MAPK8 and regulating MAPK8/ERK signal pathway.

MicroRNAs (miRs) have been demonstrated to regulate physiological and pathological processes. Numerous miRsprotect against cardiomyocyte injury induced by oxidative stress. However, the function of miR-190 still remains unclear. Here, we determined the expression level of miR-190 in H9c2 cells under H2O2 treatment and found that miR-190 expression was significantly inhibited by H2O2. Further study indicated that miR-190 significantly reduced cell apoptosisand the LDH and MDA levels of H9c2 cells induced by H2O2. Luciferase activity assay, quantitative real-time-PCR, and Western blot demonstrated that miR-190 directly targets MAPK8. Rescue experiment confirmed this hypothesis. Further study has revealed that miR-190 protects H9c2 cells from oxidative stress injury through inhibiting the MAPK8/ERK signal pathway. In conclusion, these data suggest that miR-190 protects against oxidative stress injury of H9c2 cells induced by H2O2 through inhibiting MAPK8 expression and the MAPK8/ERK pathway. Our findings provide a potential therapeutic target to promote functional recovery after cardiac ischemia/reperfusion.

MicroRNA-206 Protects against Myocardial Ischaemia-Reperfusion Injury in Rats by Targeting Gadd45ß.

MicroRNAs are widely involved in the pathogenesis of cardiovascular diseases through regulating gene expression via translational inhibition or degradation of their target mRNAs. Recent studies have indicated a critical role of microRNA-206 in myocardial ischaemia-reperfusion (I/R) injury. However, the function of miR-206 in myocardial I/R injury is currently unclear. The present study was aimed to identify the specific role of miR-206 in myocardial I/R injury and explore the underlying molecular mechanism. Our results revealed that the expression level of miR-206 was significantly decreased both in rat I/R group and H9c2 cells subjected to hypoxia/reoxygenation (H/R) compared with the corresponding control. Overexpression of miR-206 observably decreased infarct size and inhibited the cardiomyocyte apoptosis induced by I/R injury. Furthermore, bioinformatics analysis, luciferase activity and western blot assay proved that Gadd45ß (growth arrest DNA damage-inducible gene 45ß) was a direct target gene of miR-206. In addition, the expression of pro-apoptotic-related genes, such as p53, Bax and cleaved caspase3, was decreased in association with the down-regulation of Gadd45ß. In summary, this study demonstrates that miR-206 could protect against myocardial I/R injury by targeting Gadd45ß.

Inhibition of microRNA-1 attenuates hypoxia/re-oxygenation-induced apoptosis of cardiomyocytes by directly targeting Bcl-2 but not GADD45Beta.

MicroRNAs are small non-coding RNAs that are able to regulate gene expression and play important roles in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-1 exacerbated I/R-induced injury. This study was to investigate theanti-apoptotic property of miR-1 inhibition and the potential regulatory mechanism. Results showed miR-1 expression reduced in the heart of rats undergoing myocardial I/R and the cardiomyocytes receiving hypoxia/reoxygenation (H/R) injury, but the serum miR-1 expression increased. The targets of miR-1 were predicted by cDNA microarray, and Bcl-2 and GADD45ß were selected as candidate targets. Western blot assay and qPCR showed Bcl-2 and GADD45ß protein and mRNA expressions increased after I/R injury and H/R injury. Bcl-2 was a direct target of miR-1 as shown in previous studies. Luciferase assay and Western blot assay revealed GADD45ß was a direct target of miR-1, and miR-1 suppressed GADD45ß expression via binding to its 3'UTR. Furthermore, miR-1 inhibition increased Bcl-2 expression and reduced IA/AAR (infarct area/area at risk) ratio and cell apoptosis in rats undergoing myocardial I/R as well as in cardiomyocytes receiving H/R injury. Importantly, Bcl-2 knockdown restored these consequences following miR-1 inhibition. However, GADD45ß knockdown reduced IA/AAR ratio and cell apoptosis in vivo and in vitro, but failed torestore above consequences after miR-1 inhibition. In conclusion miR-1 inhibition protects against H/R-induced apoptosis of myocytes by directly targeting Bcl-2 but not GADD45ß.

Polymorphism of klotho G-395A and susceptibility of coronary artery disease in East-Asia population: a meta-analysis.

OBJECTIVE: To investigate the association between polymorphism of Klotho G-395A and susceptibility of coronary artery disease (CAD) in East-Asia population. METHODS: A total of 6 case-control studies involving 1560 patients and 1459 controls were analyzed in the study. PubMed, Embase, CBM disc, Wanfang database were searched for published case-control studies investigating the association between Klotho G-395A and CAD that were available before Dec. 2013. Fixed or random effect models were selected for odds ratio (OR) calculation. A Meta-analysis was performed to estimate heterogeneity and the pooled odds ratio (OR) to evaluate the relationship between Klotho G-395A polymorphism and CAD. The sensitivity analysis was also assessed. RESULTS: There was no significant heterogeneity found (dominant genetic model: P = 0.2, I(2) = 30.8%). The pooled OR (95% CI) value of the frequencies of the Klotho G-395A genotype (GA + AA)/GG calculated by fixed effects mode was 1.24 (95% CI:1.06-1.45), P = 0.009. There was no significant heterogeneity among the remaining articles after using random effect model or excluding the article with the largest weight or the article with larger frequencies of the allele A, respectively. And the pooled OR (95% CI) value of the frequencies of the genotype (GA + AA)/GG were similar. Publication bias was not found by Begg's test. CONCLUSION: Klotho G-395A polymorphism may be a susceptible factor of CAD in East-Asia population.