Association between ticagrelor plasma concentration and bleeding events in Chinese patients with acute coronary syndrome.

AIMS: The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events. METHODS: Patients diagnosed with acute coronary syndrome and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified. RESULTS: A total of 631 patients were included and 133 patients had bleeding academic research consortium type 1 or 2 bleeding event. The median ticagrelor concentration (interquartile range) was significantly higher in patients with bleeding events than that in patients without bleeding events (322.6 ng/mL [196.2-458.0 ng/mL] vs. 222.1 ng/mL [140.4-341.9 ng/mL], P < .001). According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (area under the curve = 0.65; P < .001, 95% Cl: 0.595-0.700). Pharmacogenomics results showed that P2Y12 (rs6787801, P = .024) and P2Y12 (rs6785930, P = .048) were statistically associated with ticagrelor levels and bleeding events, respectively. CONCLUSION: Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with acute coronary syndrome.

MiR-219a-2 relieves myocardial ischemia-reperfusion injury by reducing calcium overload and cell apoptosis through HIF1α/ NMDAR pathway.

OBJECTIVE: During the process of myocardial ischemia-reperfusion injury (MIRI), the intracellular Ca2+ concentration ([Ca2+]i) continues to increase, leads to the cardiomyocyte apoptosis and eventually causes myocardial damage, while the upstream regulation mechanism of calcium overload is still unknown. This study focuses on the role of miR-219a-2 in MIRI and aims to elaborate its regulatory mechanism on calcium overload that occurs during MIRI. METHODS: The expression of miR-219a-2 was determined in the heart tissues of MIRI mice by qRT-PCR. The [Ca2+]i was measured by fluo-3 using a fluorescence microplate reader. The expression of hypoxiainducible factor 1α (HIF1α) and NR1, the obligatory subunit of N-methyl-d-aspartate receptor 1 (NMDAR), were measured by qRT-PCR and western blot. The luciferase reporter assay was used to confirm the interplay between miR-219a-2 and HIF1α and the interplay between HIF1α and NR1. The cell apoptosis was measured by the expression level of B-cell lymphoma 2 interacting mediator of cell death (Bim) and the number of TUNEL-positive cells. The myocardial infarct size of mice was measured by TTC/Evans Blue staining. RESULTS: MiR-219a-2 was down-regulated in the heart tissues of MIRI mice. miR-219a-2 overexpression decreased [Ca2+]i and the expression of HIF1α and NR1 in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Then, the luciferase reporter assay showed that miR-219a-2 inhibited the transcription of HIF1α and HIF1α promoted the transcription of NR1. Both HIF1α overexpression and NMDAR function enhancement removed the inhibitory effect of miR-219a-2 on calcium overload and cell apoptosis in H/R-treated HL-1 cells. Finally, the overexpression of miR-219a-2 decreased Ca2+ concentration, cell apoptosis, and myocardial infarction size in MIRI mice, while the NMDAR function enhancer reversed the therapeutic effect of miR-219a-2. CONCLUSION: MiR-219a-2 reducing NMDAR-mediated calcium overload via HIF1α/NR1 axis, thus alleviating cell apoptosis in MIRI.

MiR-128/SOX7 alleviates myocardial ischemia injury by regulating IL-33/sST2 in acute myocardial infarction.

Acute myocardial infarction (AMI) induced by ischemia hypoxia severely threatens human life. Cell apoptosis of neurocytes was identified to mediate the pathogenesis, while the potential mechanism was still unclear. Sprague Dawley (SD) rats were used to establish the AMI rat model. Real-time polymerase chain reaction (PCR) and Western blot were performed to detect gene expression in mRNA and protein levels, respectively. A TUNEL assay was carried out to determine cell apoptosis. The relationship between SRY-related HMG-box (SOX7) and miR-128 was verified using luciferase reporter assay. The expression of SOX7 was decreased, while miR-128 was increased in AMI rats and ischemia hypoxia (IH) induced H9c2 cells. Hypoxia induction significantly promoted the expression of interleukin (IL)-33 and soluble ST2 (sST2), and also promoted cell apoptosis. MiR-128 targets SOX7 to regulate its expression. Down-regulated miR-128 reversed the effects of IH on expression of SOX7, sST2 and cell apoptosis, while down-regulated sST2 abolished the effects of miR-128 inhibitor. In addition, overexpressed IL-33 abolished the effects of miR-128 inhibitor that induced by IH on the expression of SOX7 and cell apoptosis. In vivo experiments validated the expression of miR-128 on cell apoptosis. The present study indicated that miR-128 modulated cell apoptosis by targeting SOX7, which was mediated by IL-33/sST2 signaling pathway.

N,N-dimethylsphingosine attenuates myocardial ischemia-reperfusion injury by recruiting regulatory T cells through PI3K/Akt pathway in mice.

N,N-dimethylsphingosine (DMS) has been documented to be in vitro protective against myocardial ischemia-reperfusion injury (IRI) and can recruit CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which may participate in the cardioprotection. We hypothesized that when in vivo applied after a myocardial ischemia, DMS may be cardioprotective by recruiting Tregs. Myocardial IRI was induced in C57BL/6 mice by occluding the left main coronary arteries followed by relaxation, and DMS (0.43 mg/kg) was intravenously injected 5 min after the onset of ischemia. We found that in wild-type (WT) mice, compared with the ischemia-reperfusion group, DMS reduced the infarct size (47.1 ± 8.9 vs. 33.1 ± 3.4 %, p < 0.01), and neutrophil infiltration at 24 h reperfusion (R) evaluated by TTC and immunohistochemical staining, respectively, and increased the aggregation of Tregs [(6 ± 1)/mm(2) vs. (30 ± 4)/mm(2), p < 0.01], peaking at 1 h R by immunofluorescence staining, with reduced gene expression of inflammatory factors at 4 h R in the reperfused myocardium by real-time PCR. This protection was abolished by phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor or Tregs-depleting antibody. Relative to WT mice, the cardioprotection conferred by T cell- and B cell- deficient Rag2 knockout (KO) mice was not strengthened by DMS or by DMS and the adoptive transfer of Tregs from WT mice, but was abolished by DMS and WT non-Tregs and was recaptured by the cotransfer with WT Tregs but not with Akt1(+/-) mice-derived Tregs. In conclusion, applied at an early stage of ischemia, DMS may be in vivo protective against myocardial IRI by recruiting Tregs via PI3K/Akt pathway.

Five-year outcomes of double kissing mini-culotte stenting vs. mini-culotte stenting using drug-eluting stents for the treatment of true coronary bifurcation lesions.

Objective: This study aimed to compare the clinical outcomes of double kissing mini-culotte (DKMC) stenting with those of mini-culotte (MC) stenting in treating patients with true coronary bifurcation lesions (CBLs) in the clinical real world. Methods: This retrospective observational cohort study included 180 consecutive patients with true CBLs (Medina type 1,1,1; 1,0,1; 0,1,1). All eligible patients underwent coronary angiography and percutaneous coronary intervention with two-stent techniques in our hospital; among them, 97 received DKMC treatment and 83 MC treatment. The primary clinical endpoints were the major adverse cardiovascular events (MACE), which included cardiac death, myocardial infarction, and target vessel/lesion revascularization (TVR/TLR). The secondary endpoints were stent thrombosis, in-stent restenosis, and individual components of MACE. Results: Quantitative coronary angiography analysis (at 5 years) revealed that late lumen loss (0.25 ± 0.41 mm vs. 0.14 ± 0.32 mm, P = 0.032) and segmental diameter restenosis of the side branch (27.84 ± 12.34% vs. 19.23 ± 9.76%, P = 0.016) were lower in the DKMC treatment group than that in the MC treatment group. Notably, compared to that in the MC treatment group, the cumulative event rate of MACE at 5 years (22.8% vs. 8.3%, P = 0.007) and TVR/TLR (17.7% vs. 6.3%, P = 0.018) was higher in the DKMC treatment group, driven mainly by TVR/TLR. Especially, the DKMC group was related to a significant reduction in the primary and secondary endpoints in high-risk patients. Conclusion: DKMC treatment was associated with less late lumen loss and restenosis in the side branch and a lower rate of cumulative MACE and TVR/TLR. DKMC treatment is more effective for treating true CBLs than MC treatment; however, these findings warrant further confirmation through a randomized clinical trial.

Necessity sequential intermediate kissing balloon dilation for crush stenting: Further insights from metal/polymer vessel scaffolds bench testing.

Sequential intermediate kissing balloon dilation (sIKBD) is crucial for crush stenting, but it require appropriate procedure remains unclear for crush stenting. This study aims to investigate whether sIKBD is necessary and how it can be properly performed during crush stenting. Mini-crush stenting (mini-CS) and sIKBD for mini-crush stenting (sIKBD-mini-CS) using metal drug-eluting stents/polymer bioresorbable vessel scaffolds (mDES/pBVS) were emulated in bifurcation models considering the branch diameter difference, and sIKBD was added to mini-CS for pretreating side-branch (SB) stent before main-branch (MB) stenting (second figure), respectively. Micro-computed tomography was used to assess the morphological parameters of bifurcated stents including length of overlapping stent segment, residual ostial stenosis of the SB, and neocarina length using quantitative methods. Further, optical coherence tomography was to analyze the incidence of stent malapposition. Quantitative analysis demonstrated that in mDES/pBVS phantom, the neocarina length (mDES: 0.45 ±â€…0.10 mm vs 0.30 ±â€…0.09 mm, P = .005; pBVS: 0.47 ±â€…0.11 mm vs 0.29 ±â€…0.09 mm, P = .001), residual ostial stenosis at the SB (mDES: 19.37 ±â€…8.21% vs 12.47 ±â€…2.05%, P = .001; pBVS: 21.89 ±â€…8.54% vs 9.98 ±â€…3.35%, P = .035), and stent malapposition in the overlapping segment (mDES: 10.29 ±â€…3.31% vs 3.83 ±â€…0.97%, P = .001; pBVS: 12.05 ±â€…3.87% vs 6.40 ±â€…1.59%, P = .003) were lower in the sIKBD-mini-CS group than those in the mini-CS group (P < .05 for all). The results of factorial analysis showed that mDES platform tended to have better morphological indicators than the pBVS platform. Adding the sIKBD to mini-CS showed better morphologic characteristics of mDES/pBVS phantoms when compared with mini-CS. Therefore, it should be considered as a critical and proper technique for crush stenting.

Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients.

Osteoprotegerin (OPG) gene polymorphisms (T245G, T950C and G1181C) have been associated with osteoporosis and early predictors of cardiovascular disease. The aim of this study was to evaluate whether these polymorphisms contribute to cardiovascular disease (CVD) in type 2 diabetic patients. We performed a case-control study with 178 CVD subjects with diabetes and 312 diabetic patients without CVD to assess the impact of variants of the OPG gene on the risk of CVD. The OPG gene polymorphisms were analyzed by using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There was no significant association between the T245G and G1181C polymorphisms and CVD in the additive genetic model (OR = 0.96, 95% CI 0.64-1.45, p = 0.79; OR = 1.06, 95% CI 0.81-1.39, p = 0.65, respectively). However, the C allele of the T950C polymorphism was independently associated with a risk of CVD in type 2 diabetic patients in this genetic model (OR = 1.38, 95% CI 1.07-1.80, p = 0.01). This study provides evidence that the C allele of the T950C polymorphism is associated with increased risk of CVD in diabetic patients. However, well-designed prospective studies with a larger sample size are needed to validate these results.

Mannose binding lectin-associated serine protease-1 is a novel contributor to myocardial ischemia/reperfusion injury.

BACKGROUND: The lectin pathway has been demonstrated to play a critical role in the pathological process of myocardial ischemia/reperfusion injury (IRI). Mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1), especially different from other components of the lectin pathway, mediates proinflammatory and procoagulant reactions independent of complement cascades. However, the role of MASP-1 in myocardial IRI remains unknown so far. METHODS: Myocardial IRI was established with 45 min ischemia and 24 h reperfusion in mice. C1 inhibitor, as the natural inhibitor of MASP-1, was administrated at 20 IU/Kg via tail vein 5 min before surgical operation. Cardiac function and myocardial infarct size were assessed. Myocardial histology and fibrosis were evaluated by H&E and Masson staining, respectively. Deposition of MASP-1, expression of PAR-1/4 and neutrophil extracellular traps (NET) were investigated on myocardium tissue by IHC staining. Cell apoptosis was detected by TUNEL assay. Levels of myocardial enzymes and proinflammatory cytokines were determined by ELISA. RESULTS: Inhibition of MASP-1 with C1 INH improved cardiac function and alleviated myocardium tissue injury (infarct size, enzymes, histology and fibrosis) after myocardial IRI. Deposition of MASP-1 and expression PAR-1, as well as NET formation in myocardial tissue were suppressed by MASP-1 inhibitor, while PAR-4 was elevated. Levels of apoptosis, HMGB-1 and IL-6 were lower after blocking MASP-1. Yet, IL-8 and TNF-α remained unchanged. CONCLUSIONS: MASP-1, as a new contributor, played a critical role in myocardial IRI. Inhibition of MASP-1 protected myocardial tissue from IRI probably via regulation of PARs/NET pathway. This may provide a novel target strategy against myocardial IRI.

Effects of diagnostic ultrasound with cRGD-microbubbles on simultaneous detection and treatment of atherosclerotic plaque in ApoE-/- mice.

Background: Atherosclerotic vulnerable plaque is the leading cause of acute fatal cardiovascular events. Thus, early rapid identification and appropriate treatment of atherosclerotic plaque maybe can prevent fatal cardiovascular events. However, few non-invasive molecular imaging techniques are currently available for the simultaneous detection and targeted treatment of atherosclerotic plaques. We hypothesized that diagnostic ultrasound (DU) combined with cyclic Arg-Gly-Asp-modified microbubbles (MBR) could provide targeted imaging and dissolution of activated platelets to identify advanced atherosclerotic plaques and improve plaque instability. Methods: Three mouse models, apolipoprotein E-deficient mice on a hypercholesterolemic diet (HCD) or normal chow diet and wild-type mice on an HCD were used. The most appropriate ultrasonic mechanical index (MI) was determined based on the expression of GP IIb/IIIa in sham, DU alone and DUMBR-treated groups at MI values of 0.5, 1.5, and 1.9. The video intensity (VI) values, activated platelets and plaque instability were analyzed by ultrasound molecular imaging, scanning electron microscopy and histopathological methods. Results: We found that the VI values of ultrasound molecular imaging of MBR were positively correlated with plaque GP IIb/IIIa expression, vulnerability index and necrotic center / fiber cap ratio. 24 h after treatment at different MIs, compared with those of the other groups, both the VI values and GP IIb/IIIa expression were significantly reduced in MI 1.5 and MI 1.9 DUMBR-treated groups. The plaque vulnerability index and necrotic center / fiber cap ratio were significantly decreased in MI 1.5-treated group, which may be due to targeted dissolution of activated platelets, with a reduction in von Willebrand factor expression. Conclusion: DUMBR targeting GP IIb/IIIa receptors could rapidly detect advanced atherosclerotic plaques and simultaneously give targeted therapy by dissolving activated and aggregated platelets. This technology may represent a novel approach for the simultaneous identification and treatment of atherosclerotic plaques.

[Retracted] IL­33 attenuates cardiac remodeling following myocardial infarction via inhibition of the p38 MAPK and NF­κB pathways.

An interested reader of an article published in the journal Circulation Research [Krishnamurthy P, Rajasingh J, Lambers E, Qin G, Losordo DW and Kishore R: L­10 inhibits inflammation and attenuates left ventricular remodeling after myocardial infarction via activation of STAT3 and suppression of HuR. Circ Res 104: e9­18, 2008] drew to our attention that data featured in their paper had appeared subsequently in the abovementioned article by Yin et al in Molecular Medicine Reports in 2014. Specifically, Fig. 1 in the Mol Med Rep paper included the same histograms as those featured in Fig. 2 in the Circ Res paper; Fig. 2 in the Mol Med Rep paper contained data derived from Fig. 1 in the Circ Res paper; and Figs. 3­5 in both papers shared a substantial amount of the same data. Following an internal investigation, the Journal was able to confirm that this accusation of plagiarism was well­founded. On those grounds, the Editor of Molecular Medicine Reports has decided to retract this paper. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor deeply regrets the grievance that this matter has caused to the authors of the previously published article, and also any inconvenience caused to the readership of the Journal.

Mental Health of Nursing Students amid Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is a global disaster, and recent studies have shown its association with increasing mental health problems such as post-traumatic stress disorder (PTSD), depression, anxiety, and stress. Nursing students, especially nursing interns, may be shunned, harassed, and even blamed as potential COVID-19 spreaders, though they were an important reserve force against COVID-19 and other diseases. Of note, the psychological influences of COVID-19 on nursing students remained unclear. The aim of this study was to evaluate the mental health of nursing students during the COVID-19 pandemic. A cross-sectional online survey was conducted on nursing students in a vocational college from April 12 to 23, 2020. The Impact of Event Scale-Revised, 21-item Depression, Anxiety and Stress Scale, and Pittsburgh Sleep Quality Index were used to assess the degree of symptoms of PTSD, depression, anxiety, stress, and insomnia, respectively. Multivariable logistic regression analysis was performed to determine the potential risk factors for the psychological symptoms. A total of 1,780 college nursing students were asked to participate in this online survey, with 1,532 complete responses. In total, 682 (44.5%) college nursing students reported having PTSD, 358 (22.8%) students reported insomnia, and few students reported depression (n = 45, 2.9%), anxiety (n = 44, 2.9%), and stress (n = 17, 1.1%) symptoms. As compared with junior, female, and rural nursing students, the senior, male, and urban nursing students had higher rates of PTSD, depression, anxiety, stress, respectively, whereas male nursing students had a higher insomnia rate. Multivariable analysis showed that senior nursing students had higher risks of PTSD, depression, anxiety; being male was associated with higher risks of PTSD, depression, anxiety, stress, and insomnia; and urban nursing students had higher risks of PTSD, depression, anxiety, and stress. In summary, a considerable number of nursing students reported mental symptoms of PTSD and insomnia, though few reported mental symptoms of depression, anxiety, and stress. Furthermore, senior, male, and urban nursing students are at risk for developing mental symptoms. Appropriate psychological interventions should be implemented to assure the mental health of nursing students.

CircDIP2C ameliorates oxidized low-density lipoprotein-induced cell dysfunction by binding to miR-556-5p to induce TET2 in human umbilical vein endothelial cells.

Circular RNAs (circRNAs) are a group of conserved noncoding RNAs. Recent reports reveal that circRNAs play vital parts in cardiovascular system, including atherosclerosis (AS). The present study is designed to reveal the role of circRNA DIP2C-disco interacting protein 2 homolog C (circDIP2C) in oxidized low-density lipoprotein (ox-LDL)-triggered damage of human umbilical vein endothelial cells (HUVECs). The expression levels of circDIP2C, microRNA-556-5p (miR-556-5p) and tet methylcytosine dioxygenase 2 (TET2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot analysis. Cell viability and angiogenesis were demonstrated by cell counting kit-8 and tube formation assays, respectively. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were checked by ROS and MDA determination assays. Superoxide dismutase (SOD) and lactate dehydrogenase (LDH) activity assays were performed to detect the activity of SOD and LDH. The binding sites of miR-556-5p in circDIP2C or TET2 were predicted by online databases, and identified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. CircDIP2C and TET2 expression were obviously decreased, while miR-556-5p expression was increased in ox-LDL-induced HUVECs in comparison with untreated HUVECs. Ox-LDL treatment inhibited cell viability and angiogenesis, promoted oxidative stress, enhanced cytotoxicity and activated NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway. CircDIP2C upregulation protected HUVECs from ox-LDL-induced injury. Additionally, circDIP2C directly bound to miR-556-5p, which was further found to target TET2. MiR-556-5p mimics or TET2 silencing could attenuate the effect of circDIP2C overexpression on ox-LDL-induced cell disorder. Thus, we came a conclusion that circDIP2C protected against ox-LDL-induced HUVEC damage by upregulating TET2 expression through sponging miR-556-5p, which provided a strategy for the therapy of AS.

LncRNA 1700020I14Rik/miR-297a/CGRP axis suppresses myocardial cell apoptosis in myocardial ischemia-reperfusion injury.

BACKGROUND: Long non-coding RNAs (lncRNAs) are closely related to various human diseases, but their role in myocardial injury has not been fully elucidated. In the current study, we found that the expression of lncRNA 1700020I14Rik was significantly down-regulated in myocardial injury tissues and the underlying mechanism by which lncRNA 1700020I14Rik regulated myocardial cell injury was investigated. METHODS: The model of myocardial ischemia-reperfusion (I/R) injury and myocardial cells hypoxia/reoxygenation (H/R) injury were established and the expression of 1700020I14Rik, miR-297a or CGRP was analyzed by qRT-PCR or Western blot. Moreover, myocardial cell apoptosis was assessed by TUNEL staining and the concentration of LDH in the mouse plasma sample or myocardial cell culture supernatant was measured by the LDH cytotoxicity test kit. Furthermore, the differences of myocardial cell survival rate after H/R treatment were assessed by MTT assay and the observation of CGRP expression was performed in HL-1 cells overexpressed or silenced with 1700020I14Rik or miR-297a. In addition, the regulating function of miR-297a on 1700020I14Rik and CGRP expression was analyzed by a dual luciferase reporter assay. RESULTS: The expressions of 1700020I14Rik and CGRP were abnormally down-regulated in a model of myocardial I/R injury and myocardial cells H/R injury, while miR-297a was up-regulated. By TUNEL staining, the apoptotic rate of myocardial cells in the model of myocardial I/R injury was significantly increased. Furthermore, the concentrations of LDH in the mouse plasma sample or myocardial cell culture supernatant were significantly increased after myocardial cell injury. By MTT assay, the survival rate of cells was decreased after myocardial cells were treated with H/R. In addition, overexpression of 1700020I14Rik or knockdown of miR-297a could up-regulate CGRP protein level, while interference with 1700020I14Rik or overexpression of miR-297a produced the opposite result. Further study confirmed that lncRNA 1700020I14Rik/miR-297a/CGRP axis suppressed myocardial cell apoptosis in myocardial I/R injury. CONCLUSION: Our results indicated that 1700020I14Rik was abnormally down-regulated in myocardial injury tissues. In-depth studies manifested that 1700020I14Rik/miR-297a/CGRP axis suppressed myocardial cell apoptosis in myocardial I/R injury.

LncRNA ANRIL knockdown relieves myocardial cell apoptosis in acute myocardial infarction by regulating IL-33/ST2.

Objective: To investigate the role of lncRNA ANRIL in the modulation of myocardial cell apoptosis in acute myocardial infarction (AMI).Methods: AMI mice model was established, and lncRNA ANRIL, IL-33 and ST2 expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The apoptosis of myocardial cells was detected by TUNEL assay. RNA pull-down and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between lncRNA ANRIL and USP17.Results: Compared with sham group, lncRNA ANRIL and ST2 expression levels were up-regulated, and the apoptosis of myocardial cells was increased in heart tissues of AMI group. Compared with normoxia group, the apoptosis of mouse myocardial cell HL-1 and primary murine myocardial cells was increased, and lncRNA ANRIL and ST2 expression levels were up-regulated in hypoxia group. We also found up-regulation of IL-33 in AMI group and hypoxia group. Besides, lncRNA ANRIL affected deubiquitinase USP17-mediated degradation of IL-33. Interfering lncRNA ANRIL reduced the apoptosis of myocardial cells through IL-33/ST2 pathway. In vivo experiments found that interfering lncRNA ANRIL relieved myocardial cell apoptosis and improved heart function in AMI mice.Conclusion: LncRNA ANRIL regulated myocardial cell apoptosis through IL-33/ST2 pathway.

Double kissing mini-culotte versus mini-culotte stenting: insights from micro-computed tomographic imaging of bench testing.

AIMS: This study aimed to evaluate the morphologic characteristics of double kissing (DK) mini-culotte and mini-culotte stenting through imaging of bench testing. METHODS AND RESULTS: DK mini-culotte and mini-culotte stenting were performed in two silicone bifurcated phantoms with branch vessel diameter differences of 0.5 mm (Model 1) and 1.25 mm (Model 2), and their morphologic characteristics were evaluated by micro-computed tomography. In Model 1, metal carina length (0.25±0.13 mm vs 0.55±0.15 mm), area stenosis of the side branch ostium (SBO) (4.65±3.24% vs 12.5±3.93%), and maximum distance of malapposed struts for the wall facing the SBO (0.27±0.08 mm vs 0.49±0.15 mm) were lower in the DK mini-culotte group than in the mini-culotte group. In Model 2, metal carina length (0.21±0.47 mm vs 0.47±0.12 mm), SBO area stenosis (5.13±3.37% vs 15.00±6.18%), and maximum distance of malapposed struts (0.32±0.13 mm vs 0.68±0.10 mm) were also lower in the DK mini-culotte group. The results of factorial analysis showed that maximum distance of malapposed struts tended to be shorter in Model 1 (F=4.226, p=0.062). CONCLUSIONS: Compared with mini-culotte stenting, DK mini-culotte stenting was associated with shorter metal carina length, shorter maximum distance of malapposed struts, and smaller SBO area stenosis. Thus, DK mini-culotte stenting may obtain better morphologic characteristics.

Visualizing polymeric bioresorbable scaffolds with three-dimensional image reconstruction using contrast-enhanced micro-computed tomography.

There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). This study aimed to explore the feasibility of detecting polymeric BRS with 3-dimensional reconstruction of BRS images by contrast-enhanced mCT and to determine the optimal imaging settings. BRSs, made of poly-L-lactic acid (PLLA), were implanted in coronary bifurcation models. Five treatments were conducted to examine an optimal condition for imaging BRSs: Baseline treatment, samples were filled with normal saline and scanned with mCT immediately; Treatment-1, -2, -3 and -4, samples were filled with contrast medium and scanned with mCT immediately and 1, 2 and 3 h thereafter, corresponding to soaking time of contrast medium of 0, 1, 2 and 3 h. Compared to Baseline, mCT scanning completely discriminate the scaffold struts from the vascular lumen immediately after filling the samples with contrast agent but not from the vascular wall until the contrast agent soaking time was more than 2 h (Treatment-3 and -4). By setting 10-15 HU as a cut-point of CT values, the scaffold strut detectable rate at Baseline and Teatment-1, -2, -3 and -4 were 1.23 ± 0.31%, 1.65 ± 0.26%, 58.14 ± 12.84%, 97.97 ± 1.43% and 98.90 ± 0.38%, respectively (Treatment-3 vs. Treatment-2, p < 0.01); meanwhile, the success rate of 3D BRS reconstruction with high quality images at Baseline and Teatment-1, -2, -3 and -4 were 1.23%, 1.65%, 58.14%, 97.97% and 98.90%, respectively (Treatment-3 vs. Treatment-2, p < 0.01). In conclusions, reconstruction of 3D BRS images is technically feasible by contrast-enhanced mCT and soaking time of contrast agent for more than 2 h is necessary for complete separation of scaffold struts from the surrounding structures in the phantom samples.

Fasting serum CGRP levels are related to calcium concentrations, but cannot be elevated by short-term calcium/vitamin D supplementation.

Calcitonin gene-related peptide (CGRP) is an important cardioprotective neuropeptide. Few studies have shown that calcium supplementation may increase CGRP levels transiently. However, the relationship between CGRP and calcium is poorly known. This study was to explore the correlation between serum calcium and CGRP in coronary artery disease (CAD), and observe whether short-term calcium/vitamin D supplementation would increase fasting serum CGRP. A randomized, placebo-controlled and double-blind clinical trial, and a supplementary study for further analysis of the correlations were conducted. The results showed that the correlation between serum calcium and CGRP was positive in CAD without myocardial infarction (MI) (r = 0.487, P = 0.029), but negative in acute and healing MI (r = -0.382, P = 0.003). Moreover, we found a positive correlation between lg (amino-terminal pro-B-type natriuretic peptide, NT-proBNP) and CGRP (r = 0.312, P = 0.027), but a negative correlation between lg (NT-proBNP) and serum calcium (r = -0.316, P = 0.025) in acute and healing MI. As to the clinical trial, participants subjected to CAD but without evolving or acute MI, together with blood calcium ≤ 2.4 mmol/L, were randomized into three groups. Among the groups of placebo, caltrate (600 mg elemental calcium; 125 IU vitamin D3, per tablet) 1 tablet/d and caltrate 2 tablets/d, there were no significant differences in baseline characteristics. After short-term (5 days) treatments, the results indicated that the effect of grouping was not statistically significant (P = 0.915). In conclusion, the correlations between serum calcium and CGRP in different types of CAD are inconsistent, and the main reason may be associated with elevated natriuretic peptides after acute MI. Further, our study shows that short-term calcium/vitamin D supplementation cannot significantly increase fasting serum CGRP levels.

Elevated Human Endothelial Cell-Specific Molecule-1 Level and Its Association With Coronary Artery Disease in Patients With Hypertension.

BACKGROUND: Endothelial dysfunction plays an important role in the pathophysiology of coronary artery disease (CAD). Previous studies suggested that human endothelial cell-specific molecule-1 (endocan) may be a novel endothelial dysfunction marker. This study aims to investigate the relationship between serum endocan level and the presence and severity of CAD in patients with hypertension. METHODS: A total of 190 eligible hypertension patients were enrolled in this study. Serum endocan level was measured by enzyme-linked immunosorbent assay. The presence and severity of CAD were evaluated by coronary angiography. RESULTS: Hypertensive patients with CAD had significantly higher serum endocan level than those without CAD (1.63 ± 0.51 ng/mL vs 1.31 ± 0.65 ng/mL, P < 0.05). Multivariate logistic regression revealed that serum endocan level was independently associated with the presence of CAD (odds ratio, 2.662; 95% confidence interval, 1.560-4.544; P < 0.001). Spearman rank correlation analysis demonstrated that serum endocan level was associated with SYNergy between PCI with TAXUS and Cardiac Surgery score (r = 0.349, P = 0.001). CONCLUSIONS: Serum endocan level is independently correlated with the presence and severity of CAD in hypertension patients, and those with high endocan level may have an increased risk of developing atherosclerosis.

IL-33 attenuates cardiac remodeling following myocardial infarction via inhibition of the p38 MAPK and NF-κB pathways.

The inflammatory response has adverse effects on left ventricular (LV) function and remodeling post-myocardial infarction (MI). Interleukin (IL)-33 is considered to have anti-inflammatory properties. The present study examined whether the suppression of inflammation with IL-33 was able to attenuate LV dysfunction and remodeling post-MI. The MI model was induced and the mice were treated with either saline or recombinant IL-33. Inflammatory mediators, LV functional changes and structural remodeling were evaluated. IL-33 significantly suppressed macrophage infiltration and the production of inflammatory cytokines in the myocardium. IL-33 treatment significantly improved LV function, reduced infarct size and infarct wall thinning. MI-induced activation of the p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-κB (NF-κB) pathways was also suppressed. Our data demonstrated that IL-33 suppresses inflammatory responses and improved LV function and remodeling by inhibiting the p38 MAPK and NF-κB pathways. IL-33 may be a potential therapeutic target for heart dysfunction post-MI.