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1.
Oxid Med Cell Longev ; 2021: 6699516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613824

RESUMO

Coronary artery no-reflow is a complex problem in the area of reperfusion therapy, and the molecular mechanisms underlying coronary artery no-reflow injury have not been fully elucidated. In the present study, we explored whether oxidative stress caused damage to coronary endothelial cells by inducing mitochondrial fission and activating the JNK pathway. The hypoxia/reoxygenation (H/R) model was induced in vitro to mimic coronary endothelial no-reflow injury, and mitochondrial fission, mitochondrial function, and endothelial cell viability were analyzed using western blotting, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Our data indicated that reactive oxygen species (ROS) were significantly induced upon H/R injury, and this was followed by decreased endothelial cell viability. Mitochondrial fission was induced and mitochondrial bioenergetics were impaired in cardiac endothelial cells after H/R injury. Neutralization of ROS reduced mitochondrial fission and protected mitochondrial function against H/R injury. Our results also demonstrated that ROS stimulated mitochondrial fission via JNK-mediated Drp1 phosphorylation. These findings indicate that the ROS-JNK-Drp1 signaling pathway may be one of the molecular mechanisms underlying endothelial cell damage during H/R injury. Novel treatments for coronary no-reflow injury may involve targeting mitochondrial fission and the JNK-Drp1 signaling pathway.

2.
Nutr Metab Cardiovasc Dis ; 31(1): 145-152, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33500103

RESUMO

BACKGROUND AND AIMS: Healed plaque is a hallmark of previous regional plaque rupture or erosion. We hypothesized that the plasma level of trimethylamine N-oxide (TMAO) is related to healed culprit plaque in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: A prospective cohort of 206 patients with STEMI, who were examined by optical coherence tomography (OCT) was enrolled in our study. After exclusion, 156 patients were categorized into healed plaque (n = 54) and nonhealed plaque (n = 102) groups. Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry in these two groups. Increased age and low BMI were more common in patients with healed plaques than in those without healed plaques. Through OCT observation, plaque rupture (81.5% vs. 45.1%, p < 0.001), thin cap fibroatheroma (TCFA) and macrophages (42.6% vs. 20.6%, p = 0.004, 70.4% vs. 26.5%, p < 0.001, respectively) were more frequently seen in patients with healed plaques than in those without healed plaques. The TMAO level in patients with healed plaques was significantly higher than that in patients with nonhealed plaques (3.9 µM [2.6-5.1] vs. 1.8 µM [1.0-2.7], p < 0.001). Furthermore, the receiver operating characteristic curve showed that TMAO can be used as a potential biomarker to predict healed plaque presence with a cutoff value of 2.9 µM (AUC = 0.810, sensitivity: 72.2%, specificity: 81.4%). CONCLUSIONS: Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation. A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.

3.
Postgrad Med ; : 1-7, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33131368

RESUMO

Objective: The current study was to evaluate the association of Lipoprotein (a) [Lp(a)] and in-hospital outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Methods: ACS patients undergoing PCI were retrospectively enrolled. Based on Lp(a) level, patients were divided into low (<30 mg/dL) and high (≥30 mg/dL) Lp(a) groups. Results: Compared to those with low Lp(a), patients with high Lp(a) had larger numbers of coronary arteries ≥70% stenosis and had longer coronary artery lesion (P < 0.05). After adjustment for covariates, high Lp(a) remained associated with higher odds of having coronary artery ≥70% stenosis, type C coronary lesion and pre-PCI TIMI flow grade 1/0. Patients with high Lp(a) had a higher unadjusted odds of acute stent thrombosis (odds ratio [OR] 1.10 and 95% confidence interval [CI] 1.01-2.27), congestive heart failure (OR 1.24 and 95% CI 1.15-2.38) and composite in-hospital outcomes (OR 1.28 and 95% CI 1.18-2.42). After adjustment for covariates, patients with high Lp(a) still had a higher odds of congestive heart failure (OR 1.08 and 95% CI 1.01-1.78) and composite in-hospital outcomes (OR 1.12 and 95% CI 1.04-1.81). Conclusion: In ACS patients undergoing PCI, compared to those with low Lp(a), patients with high Lp(a) had more severe coronary artery lesion, higher risk of congestive heart failure and composite in-hospital outcomes.

4.
Genomics ; 113(1 Pt 1): 1-10, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33253792

RESUMO

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are the two major pathological phenotypes in acute coronary syndrome. Since microRNAs have been found to be involved in the mechanisms of PR and PE, we investigated the diagnostic utility of microRNAs in differentiating between patients with PR and patients with PE. METHODS: MicroRNA sequencing was performed on plasma from 21 patients with PR, 20 patients with PE and 17 healthy control subjects (HCs). 24 miRNAs were selected for validation in 20 PR patients and 20 PE patients and 8 miRNAs were further validated in an independent replication cohort (82 patients with PR, 84 patients with PE and 59 HCs) by applying quantitative real-time polymerase chain reaction. Then we analyzed pathways associated with significant miRNAs in PR. RESULTS: MiR-744-3p, miR-324-3p and miR-330-3p were significantly upregulated in the PR group compared with the PE group (Log10miR-744-3p: 0.26[--0.28-1.57] versus -0.41[-0.83--0.03], padj < 0.001; Log10miR-324-3p: 0.40[-0.09-0.84] versus -0.12[-0.53-0.29], padj < 0.001; Log10miR-330-3p: 0.34[0.08-0.93] versus -0.07[-0.65-0.22], padj < 0.001), The area under the receiver operating characteristic curve for the combination of these three miRNAs in distinguishing between PR from PE in training and test set was 0.764 (0.679-0.850, sensitivity = 86.2%, specificity = 54.4%, P < 0.001) and 0.768 (0.637-0.898, sensitivity,65.4%, specificity:80.0%, P = 0.001), respectively. CONCLUSION: A set of circulating microRNAs (miR-744-3p, miR-330-3p, and miR-324-3p) is associated with PR and has clinical utility as a diagnostic marker for distinguishing the plaque phenotype in STEMI patients.

5.
J Recept Signal Transduct Res ; : 1-5, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33045879

RESUMO

Coronary no-reflow damage is caused by endothelial cell damage although little drug is available to intervene in coronary no-reflow. Liraglutide is a kind of anti-diabetic drug and its cardioprotective role has been widely reported. In this study, we explored the role of liraglutide in regulating coronary endothelial cell damage. We used hydrogen peroxide to mimic coronary no-reflow damage in vitro. After exposure to hydrogen peroxide, endothelial cells' viability was significantly reduced, an effect that was followed by an increase in cell apoptosis. Interestingly, liraglutide treatment obviously upregulated endothelial cell viability and thus prevented cell apoptosis. Further, we also found that liraglutide inhibited the activation of caspase-3 in hydrogen peroxide-treated endothelial cells. Besides, cellular metabolism, as reflected by mitochondrial membrane potential, was disrupted by hydrogen peroxide and reversed to normal levels with liraglutide. Further, we found that the ERK pathway is a potential downstream effector of liraglutide. Administration of liraglutide significantly promoted the activation of ERK and this effect may contribute to endothelial cell survival. Altogether, our results illustrated that hydrogen peroxide-mediated endothelial cell damage could be attenuated by liraglutide through modulation of the MAPK/ERK signaling pathway. This finding will pave a novel road for the intervention of coronary no-reflow damage in patients suffering from myocardial infarction.

6.
J Interv Cardiol ; 2020: 4793178, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774185

RESUMO

Background: Circulating levels of cardiac troponin I (cTnI) after ST-segment elevation myocardial infarction (STEMI) were considered as prognostic factors for predicting the incidence of major adverse cardiovascular events (MACE). △cTnI is the difference between peak cTnI after primary percutaneous coronary intervention (PPCI) and cTnI on initial admission. Purpose: This study aimed to assess the relationship between △cTnI, the ratio of △cTnI to cTnI on initial admission, and the incidence of MACE during the follow-up period. Methods: A total of 2596 patients with cTnI measured upon admission and one-time measurement of cTnI during hospitalization were enrolled. Results: In the adjusted models of the survival receiver operating characteristic (ROC) curve, △cTnI and the ratio of △cTnI to cTnI on initial admission have stronger discrimination power of MACE (area under curve (AUC) 0.730 and 0.717) compared with peak cTnI after PPCI and cTnI at admission (AUC 0.590, 0.546). Multivariate Cox regression analysis identified △cTnI (hazard ratio (HR) 1.018, 95% confidence interval (CI) 1.001 to 1.035) as a relevant factor for MACE during follow-up. △cTnI was divided into quartiles, and maximum △ cTnI between 4.845 and 19.073 ng/ml comprised more patients with anterior wall myocardial infarction (p < 0.001), higher GRACE score (p = 0.038), CK-MB (p = 0.023), and Myoglobin (p < 0.001). On the K-M survival curves, the incidence of MACE, mortality, and angina pectoris were significantly higher in the group with maximum △cTnI (p = 0.035, 0.049, 0.026). Conclusion: The △cTnI level and the ratio of △cTnI have stronger discrimination power of predicting the incidence of MACE. The group with maximum △cTnI has higher incidence of MACE, mortality, and angina pectoris during the follow-up period.

7.
Nat Commun ; 11(1): 4252, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843628

RESUMO

The 2019 novel respiratory virus (SARS-CoV-2) causes COVID-19 with rapid global socioeconomic disruptions and disease burden to healthcare. The COVID-19 and previous emerging virus outbreaks highlight the urgent need for broad-spectrum antivirals. Here, we show that a defensin-like peptide P9R exhibited potent antiviral activity against pH-dependent viruses that require endosomal acidification for virus infection, including the enveloped pandemic A(H1N1)pdm09 virus, avian influenza A(H7N9) virus, coronaviruses (SARS-CoV-2, MERS-CoV and SARS-CoV), and the non-enveloped rhinovirus. P9R can significantly protect mice from lethal challenge by A(H1N1)pdm09 virus and shows low possibility to cause drug-resistant virus. Mechanistic studies indicate that the antiviral activity of P9R depends on the direct binding to viruses and the inhibition of virus-host endosomal acidification, which provides a proof of concept that virus-binding alkaline peptides can broadly inhibit pH-dependent viruses. These results suggest that the dual-functional virus- and host-targeting P9R can be a promising candidate for combating pH-dependent respiratory viruses.


Assuntos
Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Vírus da Influenza A/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Antivirais/química , Antivirais/metabolismo , Antivirais/uso terapêutico , Linhagem Celular , Endossomos/química , Endossomos/efeitos dos fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Vírus da Influenza A/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/uso terapêutico , Ligação Proteica , Conformação Proteica , Rhinovirus/efeitos dos fármacos , Rhinovirus/metabolismo , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
8.
J Diabetes Res ; 2020: 1763567, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685552

RESUMO

Background: Hyperglycemia is frequently observed in acute myocardial infarction (AMI). Diabetes mellitus (DM) patients and non-DM patients have different culprit lesion phenotypes and few data are available on non-DM patients with admission hyperglycemia. Therefore, we aimed to investigate the association between admission hyperglycemia and culprit lesion characteristics using optical coherence tomography (OCT) in AMI patients. Methods and Results: We consecutively enrolled 434 patients with AMI, and 277 patients were included in analysis: 65.7% (n = 182) non-DM patients and 34.3% (n = 95) DM patients. We measured acute blood glucose (ABG) and hemoglobin A1c to calculate the acute-to-chronic glycemic ratio (A/C). Then, we grouped non-DM patients into tertiles of A/C. OCT-based culprit lesion characteristics were compared across A/C tertiles in non-DM patients and between DM and non-DM patients. Non-DM patients had fewer lipid-rich plaques (52.7% versus 68.4%, p = 0.012) and thin-cap fibroatheroma (TCFA) (19.8% versus 34.7%, p = 0.006) than DM patients but similar prevalence of plaque rupture (47.3% versus 56.8%, p = 0.130). Non-DM patients with the highest A/C tertile had the highest prevalence of plaque rupture (p for trend = 0.002), lipid-rich plaque (p for trend = 0.001), and TCFA (p for trend = 0.003). A/C > 1.22 but not ABG > 140 mg/dl predicted a high prevalence of plaque rupture, lipid-rich plaque, and TCFA in non-DM patients. Conclusions: In AMI patients without DM, admission hyperglycemia is associated with vulnerable culprit lesion characteristics, and A/C is a better predictor for vulnerable culprit plaque characteristics than ABG. These results call for a tailored evaluation and management of glucose metabolism in nondiabetic AMI patients. This trial is registered with NCT03593928.

9.
Can J Cardiol ; 36(8): 1252-1260, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32595007

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO) has been shown to promote the development of atherosclerosis. However, the relationship between plasma TMAO and neoatherosclerosis, an important underlying mechanism of very late stent thrombosis (VLST), is unknown. METHODS: This post hoc study investigated the association between TMAO and neoatherosclerosis in 2 independent cohorts. These included a control group of 50 healthy volunteers and a study cohort of 50 patients with VLST who presented with ST-segment elevation myocardial infarction and underwent optical coherence tomography examination. Of the 50 patients with VLST, 23 had neoatherosclerosis and 27 did not have neoatherosclerosis. Patients with neoatherosclerosis were further divided into 2 subgroups, including 14 patients with plaque rupture and 9 without plaque rupture. RESULTS: The plasma TMAO levels, detected using mass spectrometry, were significantly higher in patients with VLST than in healthy individuals (median [interquartile range], 2.50 [1.67-3.84] vs 1.32 [0.86-2.44] µM; P < 0.001). Among the patients with VLST, the plasma TMAO levels were significantly higher in patients with neoatherosclerosis than in those without neoatherosclerosis (3.69 [2.46-5.29] vs 1.96 [1.39-2.80] µM; P < 0.001). In addition, in patients with neoatherosclerosis, patients with plaque rupture had significantly higher plasma TMAO concentrations than those without plaque rupture (4.51 [3.41-5.85] vs 2.46 [2.05-3.55] µM; P = 0.005). Multivariate analysis indicated that TMAO was an independent predictor of neoatherosclerosis (odds ratio, 3.41; 95% confidence interval, 1.59-7.30; P = 0.002). Moreover, the area under the receiver operating characteristic curve for TMAO, differentiated by neoatherosclerosis, was 0.85. CONCLUSIONS: Plasma TMAO was significantly correlated with neoatherosclerosis and plaque rupture in patients with VLST.

10.
Cardiovasc Drugs Ther ; 34(5): 677-684, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32572652

RESUMO

PURPOSE: To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI). METHODS: A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period. RESULTS: After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group. CONCLUSION: Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.


Assuntos
Síndrome Coronariana Aguda/terapia , Clopidogrel/uso terapêutico , Trombose Coronária/prevenção & controle , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Stents , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Clopidogrel/efeitos adversos , Trombose Coronária/etiologia , Trombose Coronária/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Mediators Inflamm ; 2020: 9343475, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32377168

RESUMO

Background: Inflammation poses dual effects after myocardial infarction, but robust evidence shows that high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, is constantly associated with worse outcomes. This study is aimed at investigating the probable nonlinear association between postprocedural hsCRP and mortality in patients with acute coronary syndromes (ACS) treated by percutaneous coronary intervention (PCI). Methods: A total of 3940 consecutive ACS patients treated by PCI with postprocedural hsCRP measurements were retrospectively recruited. Patients were stratified into 5 groups according to quintiles of hsCRP. Cox regression with adjustments for multiple covariates was used for outcome analysis. Restricted cubic spline (RCS) analysis was used to allow possible nonlinear associations. The primary outcome was all-cause death. Results: During a median follow-up of 727 days, mortality occurred in 207 (5.3%) patients. Adjusted hazard ratio (HR) was higher in the lowest (<2.26 mg/L, HR: 1.90, 95% confidence interval (CI): 1.08-3.33; P = 0.025), second highest (10.16-12.56 mg/L, HR: 1.86, 95% CI: 1.09-3.16; P = 0.023), and highest quintiles (≥12.56 mg/L, HR: 2.02, 95% CI: 1.21-3.36; P = 0.007) of postprocedural hsCRP, compared to the second lowest quintile (2.26-4.85 mg/L). RCS analysis depicted a J-shaped association between postprocedural hsCRP and mortality (P for nonlinearity = 0.004). Similar association was observed between hsCRP and cardiac death (P for nonlinearity = 0.014), but not for noncardiac mortality (P for nonlinearity = 0.228). Conclusions: Both low and high postprocedural hsCRP were associated with higher risk of death in ACS patients treated by PCI.

13.
J Cardiovasc Transl Res ; 13(6): 908-915, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32314165

RESUMO

We aimed to investigate the association between plasma myeloperoxidase (MPO) and plaque erosion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Two hundred and fifty-two patients with STEMI who underwent optical coherence tomography (OCT) evaluation of culprit lesion were prospectively enrolled. Of them, 92 and 80 patients were identified with plaque rupture and plaque erosion, respectively. Plasma MPO levels, measured using enzyme-linked immunoassay, were significantly higher in patients with plaque erosion versus plaque rupture (median (interquartile range), 96.3 ng/mL [44.2-173.3] vs. 41.7 ng/mL (29.2-66.3); p < 0.001). Multivariable logistic regression analysis indicated that plasma MPO was independently associated with plaque erosion (odds ratio, 3.25; 95% confidence interval, 1.37-7.76; p = 0.008). The area under the receiver-operating characteristic curve was 0.75 for MPO to discriminate between plaque erosion and plaque rupture. Plasma MPO level significantly correlated with plaque erosion in patients with STEMI.

14.
J Clin Microbiol ; 58(5)2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32132187

RESUMO

Accurate detection of influenza A virus (IAV) is crucial for patient management, infection control, and epidemiological surveillance. The World Health Organization and the Centers for Disease Control and Prevention have recommended using the M gene as the diagnostic gene target for reverse-transcription-PCR (RT-PCR). However, M gene RT-PCR has reduced sensitivity for recent IAV due to novel gene mutations. Here, we sought to identify novel diagnostic targets for the molecular detection of IAV using long-read third-generation sequencing. Direct nanopore sequencing from 18 nasopharyngeal specimens and one saliva specimen showed that the 5' and 3' ends of the PB2 gene and the entire NS gene were highly abundant. Primers selected for PB2 and NS genes were well matched with seasonal or avian IAV gene sequences. Our novel PB2 and NS gene real-time RT-PCR assays showed limits of detection similar to or lower than that of M gene RT-PCR and achieved 100% sensitivity and specificity in the detection of A(H1N1), A(H3N2), and A(H7N9) in nasopharyngeal and saliva specimens. For 10 patients with IAV detected by M gene RT-PCR conversion in sequentially collected specimens, NS and/or PB2 gene RT-PCR was positive in 2 (20%) of the initial specimens that were missed by M gene RT-PCR. In conclusion, we have shown that PB2 or NS gene RT-PCRs are suitable alternatives to the recommended M gene RT-PCR for diagnosis of IAV. Long-read nanopore sequencing facilitates the identification of novel diagnostic targets.

15.
Platelets ; 31(6): 788-794, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31645164

RESUMO

Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients' adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75-100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75-100 mg (n = 744) and 50 mg (n = 322). The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared between the two groups. MACEs risk was not significantly different between the two groups (OR = 0.563, 95% CI: 0.244-1.300, P = .179). However, 50 mg aspirin was associated with a lower risk of any Bleeding Academic Research Consortium (BARC) bleeding events (OR = 0.605, 95% CI: 0.399-0.713, P = .001), also lower BARC bleeding events (OR = 0.639, 95% CI: 0.468-0.872, P = .005). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR = 0.459, 95% CI: 0.279-0.754, P = .002), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR = 0.378, 95% CI: 0.156-0.916, P = .031). After propensity score matching (PSM), a total of 317 patients in each group were matched. The MACEs composite was not significantly different between the two matched groups and 50 mg aspirin was associated with a lower risk of bleeding events and low ticagrelor withdrawal before and after multivariate adjustment. In conclusion, among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75-100 mg aspirin daily.

16.
Cardiovasc Diabetol ; 18(1): 136, 2019 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-31629406

RESUMO

BACKGROUND: Diabetes mellitus (DM) or pre-diabetes status is closely associated with features of vulnerable coronary lesions in patients with stable coronary heart disease or acute coronary syndrome. However, the association between duration of diabetes and the morphologies and features of vulnerable plaques has not been fully investigated in patients with acute myocardial infarction (AMI). METHODS: We enrolled a total of 279 patients who presented with AMI between March 2017 and March 2019 and underwent pre-intervention optical coherence tomography imaging of culprit lesions. Patients with DM were divided into two subgroups: a Short-DM group with DM duration of < 10 years and a Long-DM group with DM duration of ≥ 10 years. Baseline clinical data and culprit-plaque characteristics were compared between patients without DM (the non-DM group), those in the Short-DM group, and those in the Long-DM group. RESULTS: Patients with DM represented 34.1% of the study population (95 patients). The Short- and Long-DM groups included 64 (67.4%) and 31 patients (32.6%), respectively. Glycated hemoglobin A1c (HbA1c) levels were significantly higher in the Long-DM group than the Non- or Short-DM groups (8.4% [Long-DM] versus 5.7% [Non-DM] and 7.6% [Short-DM], P < 0.001). In addition, the highest prevalence of lipid-rich plaques, thin-cap fibroatheroma (TCFA), and plaque ruptures of culprit lesions were observed in the Long-DM group (lipid-rich plaques: 80.6% [Long-DM] versus 52.2% [Non-DM] and 62.5% [Short-DM], P = 0.007; TCFA: 41.9% [Long-DM] versus 19.6% [Non-DM] and 31.3% [Short-DM], P = 0.012; plaque rupture: 74.2% [Long-DM] versus 46.7% [Non-DM] and 48.4% [Short-DM], P = 0.017). The frequency of calcification was significantly higher among patients with DM than among those without (62.1% versus 46.2%, P = 0.016); however, no significant differences were found between the DM subgroups (61.3% [Long-DM] versus 62.5% [Short-DM], P = 0.999). CONCLUSIONS: Increased duration of DM combined with higher HbA1c levels influences culprit-plaque characteristics in patients with DM who suffer AMI. These findings might account for the higher risks of cardiac death in DM patients with long disease duration. Trial registration This study is registered at clinicaltrials.gov as NCT03593928.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada/metabolismo , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Ruptura Espontânea , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Fatores de Tempo , Regulação para Cima
17.
Emerg Microbes Infect ; 8(1): 662-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31084471

RESUMO

Influenza defective interfering (DI) particles are replication-incompetent viruses carrying large internal deletion in the genome. The loss of essential genetic information causes abortive viral replication, which can be rescued by co-infection with a helper virus that possesses an intact genome. Despite reports of DI particles present in seasonal influenza A H1N1 infections, their existence in human infections by the avian influenza A viruses, such as H7N9, has not been studied. Here we report the ubiquitous presence of DI-RNAs in nasopharyngeal aspirates of H7N9-infected patients. Single Molecule Real Time (SMRT) sequencing was first applied and long-read sequencing analysis showed that a variety of H7N9 DI-RNA species were present in the patient samples and human bronchial epithelial cells. In several abundantly expressed DI-RNA species, long overlapping sequences have been identified around at the breakpoint region and the other side of deleted region. Influenza DI-RNA is known as a defective viral RNA with single large internal deletion. Beneficial to the long-read property of SMRT sequencing, double and triple internal deletions were identified in half of the DI-RNA species. In addition, we examined the expression of DI-RNAs in mice infected with sublethal dose of H7N9 virus at different time points. Interestingly, DI-RNAs were abundantly expressed as early as day 2 post-infection. Taken together, we reveal the diversity and characteristics of DI-RNAs found in H7N9-infected patients, cells and animals. Further investigations on this overwhelming generation of DI-RNA may provide important insights into the understanding of H7N9 viral replication and pathogenesis.


Assuntos
Vírus Defeituosos/genética , Subtipo H7N9 do Vírus da Influenza A/crescimento & desenvolvimento , Influenza Humana/patologia , Influenza Humana/virologia , RNA Viral/genética , Análise de Sequência de DNA , Animais , Brônquios/virologia , Vírus Defeituosos/isolamento & purificação , Modelos Animais de Doenças , Células Epiteliais/virologia , Genoma Viral , Humanos , Camundongos , Nasofaringe/patologia , Nasofaringe/virologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , RNA Viral/isolamento & purificação , Deleção de Sequência
18.
Circ Cardiovasc Interv ; 12(1): e007281, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30599768

RESUMO

BACKGROUND: Trimethylamine N-oxide (TMAO) is reported to promote the pathogenesis of atherosclerosis and be associated with cardiovascular events risk. It is unknown whether plasma TMAO is associated with plaque morphology in patients with acute myocardial infarction. We investigated the relationship between the culprit plaque morphology and plasma TMAO concentration in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: A prospective series of 211 patients with ST-segment-elevation myocardial infarction who underwent preintervention optical coherence tomography examination for the culprit lesion were enrolled; 77 and 69 patients were categorized as plaque rupture and plaque erosion, respectively. Plasma TMAO levels, detected using stable isotope dilution liquid chromatography tandem mass spectrometry, were significantly higher in patients with plaque rupture than in those with plaque erosion (3.33 µM; interquartile range: 2.48-4.57 versus 1.21 µM; interquartile range: 0.86-1.91; P<0.001). After adjustments for traditional risk factors, elevated TMAO levels remained independently correlated with plaque rupture (adjusted odds ratio: 4.06, 95% CI, 2.38-6.91; P<0.001). The area under the receiver operating characteristic curve for plaque rupture versus plaque erosion was 0.89. At a cutoff level of 1.95 µM, TMAO had a sensitivity of 88.3% and specificity of 76.8% in discriminating plaque rupture from plaque erosion. CONCLUSIONS: High levels of plasma TMAO independently correlated with plaque rupture in patients with ST-segment-elevation myocardial infarction. Moreover, TMAO might be a useful biomarker for plaque rupture to improve risk stratification and management in patients with ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03593928.


Assuntos
Doença da Artéria Coronariana/sangue , Metilaminas/sangue , Placa Aterosclerótica , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Idoso , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Ruptura Espontânea , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Espectrometria de Massas em Tandem , Tomografia de Coerência Óptica , Regulação para Cima
19.
Am J Cardiol ; 123(6): 894-898, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30594289

RESUMO

The gut microbial metabolite trimethylamine N-oxide (TMAO) promotes atherosclerosis and cardiovascular diseases. TMAO levels are associated with the coronary atherosclerotic burden in patients with stable coronary artery disease. However, the relation between TMAO levels and the coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We prospectively enrolled 2 cohorts in this study, including 335 patients with STEMI and 53 healthy controls. The coronary atherosclerotic burden was quantified by the number of diseased coronary arteries and the SYNTAX score. The median TMAO levels in patients with STEMI and healthy controls were 2.18 (interquartile range [IQR]: 1.34 to 3.90) µM and 1.23 [IQR: 0.84 to 2.42] µM, respectively. Of the 335 patients with STEMI, TMAO levels were significantly higher in the multivessel disease group than in the single-vessel disease group (p <0.001) and in the group with intermediate-high SYNTAX scores (SYNTAX score ≥23) than in the group with low SYNTAX scores (SYNTAX score ≤22; p <0.001). Based on the ordinal logistic regression analysis adjusted for traditional risk factors, elevated TMAO levels predicted both a high SYNTAX score (adjusted odds ratio [OR]: 1.16; 95% confidence interval [CI] 1.06 to 1.29; p = 0.001) and the presence of multivessel disease (adjusted OR: 1.15; 95% CI 1.01 to 1.32; p = 0.035). In conclusion, plasma TMAO levels are associated with a high coronary atherosclerotic burden in patients with STEMI.


Assuntos
Aterosclerose/sangue , Doença da Artéria Coronariana/sangue , Vasos Coronários/diagnóstico por imagem , Metilaminas/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Aterosclerose/complicações , Aterosclerose/diagnóstico , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Índice de Gravidade de Doença
20.
Antiviral Res ; 161: 125-133, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30503888

RESUMO

Human respiratory syncytial virus (HRSV) infection is a significant cause of morbidity and mortality, particularly among the children and the elderly. Despite extensive efforts, there is currently no formally approved vaccine and effective antiviral options against HRSV infection are limited. The development of vaccines and antiviral strategies for HRSV was partly hampered by the lack of an efficient lethal mouse model to evaluate the efficacy of the candidate vaccines or antivirals. In this study, we established a lethal HRSV mouse model by consecutively passaging a clinical HRSV isolate, GZ08-0. GZ08-18 was isolated from mouse bronchioalveolar lavage fluids at the 50th passage of GZ08-0. Importantly, all GZ08-18-inoculated mice succumbed to the infection by day 7 post infection, whereas all GZ08-0-inoculated mice recovered from the infection. Subsequent investigations demonstrated that GZ08-18 replicated to a higher titer in mouse lungs, induced more prominent lung pathology, and resulted in higher expression levels of a number of key pro-inflammatory cytokines including IFN-γ, MIP-1α, and TNF-α in comparison to that of GZ08-0. The cyclophosphamide pretreatment rendered the mice more susceptible to a lethal outcome with less rounds of virus inoculation. Full genome sequencing revealed 17 mutations in GZ08-18, some of which might account for the dramatically increased pathogenicity over GZ08-0. In addition, by using ribavirin as a positive control, we demonstrated the potential application of this lethal mouse model as a tool in HRSV investigations. Overall, we have successfully established a practical lethal mouse model for HRSV with a mouse-adapted virus, which may facilitate future in vivo studies on the evaluation of candidate vaccines and drugs against HRSV.


Assuntos
Envelhecimento , Modelos Animais de Doenças , Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sincicial Respiratório Humano/patogenicidade , Animais , Antivirais/uso terapêutico , Linhagem Celular , Ciclofosfamida/farmacologia , Genoma Viral , Humanos , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Mutação , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Vírus Sincicial Respiratório Humano/fisiologia , Ribavirina/uso terapêutico , Replicação Viral
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