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1.
Bioact Mater ; 20: 286-305, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35702609

RESUMO

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have an irreplaceable role in the treatment of myocardial infarction (MI), which can be injected into the transplanted area with new cardiomyocytes (Cardiomyocytes, CMs), and improve myocardial function. However, the immaturity of the structure and function of iPSC-CMs is the main bottleneck at present. Since collagen participates in the formation of extracellular matrix (ECM), we synthesized nano colloidal gelatin (Gel) with collagen as the main component, and confirmed that the biomaterial has good biocompatibility and is suitable for cellular in vitro growth. Subsequently, we combined the PI3K/AKT/mTOR pathway inhibitor BEZ-235 with Gel and found that the two combined increased the sarcomere length and action potential amplitude (APA) of iPSC-CMs, and improved the Ca2+ processing ability, the maturation of mitochondrial morphological structure and metabolic function. Not only that, Gel can also prolong the retention rate of iPSC-CMs in the myocardium and increase the expression of Cx43 and angiogenesis in the transplanted area of mature iPSC-CMs, which also provides a reliable basis for the subsequent treatment of mature iPSC-CMs.

2.
Stroke ; 53(7): 2131-2141, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35674043

RESUMO

Cardiovascular events after primary intracerebral hemorrhage (ICH) have emerged as a leading cause of poor functional outcomes and mortality during the long-term recovery after an ICH. These events encompass arterial ischemic events such as ischemic stroke and myocardial infarction, arterial hemorrhagic events that include recurrent ICH, and venous thrombotic events such as venous thromboembolism. The purpose of this review is to summarize the cardiovascular complications after ICH, epidemiology and associated risk factors, and their impact on ICH outcomes. Additionally, we will highlight possible pathophysiological mechanisms to explain the short- and long-term increased risks of ischemic and hemorrhagic events after ICH. Finally, we will highlight potential secondary stroke and venous thrombotic prevention strategies often not considered after ICH, balanced against the risk of ICH recurrence.

3.
Cardiovasc Toxicol ; 22(8): 689-700, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35699870

RESUMO

An increasing amount of evidence has suggested that microRNA (miR) plays a role in myocardial infarction (MI). Our study aimed to discuss the impact of exosomal miR-29b-3p in MI by regulating A Disintegrin and Metalloproteinase with Thrombospondin Motifs 16 (ADAMTS16). Exosomes were extracted from bone marrow mesenchymal stem cells (BMSCs). In a rat model of MI, myocardial angiogenesis and ventricular remodeling-related factors, as well as myocardial fibrosis, collagen volume fraction (CVF), capillary density, level of vascular endothelial growth factor (VEGF), and apoptosis of cardiomyocytes, were tested. ADAMTS16 and miR-29b-3p levels in the myocardial tissue of MI rats were tested. miR-29b-3p expression was decreased and ADAMTS16 expression was increased in the myocardial tissue of MI rats. ADAMTS16 was a target gene of miR-29b-3p. Upregulated miR-29b-3p delivered by BMSC-derived exosomes improved myocardial angiogenesis and ventricular remodeling, reduced myocardial fibrosis and CVF, increased capillary density and VEGF expression, and suppressed apoptosis of cardiomyocytes in MI rats. ADAMTS16 overexpression accelerated MI in rats, and ADAMTS16 upregulation reversed the protective effects of miR-29b-3p upregulation on MI rats. Our study provides evidence that upregulated miR-29b-3p delivered by BMSC-secreted exosomes can improve myocardial angiogenesis and ventricular remodeling in rats with MI by targeting ADAMTS16.

4.
Eur J Pharmacol ; 928: 175094, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35714691

RESUMO

Morphine is generally used in clinical treatment for the patients who have not been effectively alleviated for chest pain after the treatment with nitrites or who contraindicate nitrite drugs. However, it was reported that the treatment with morphine in acute myocardial infarction or acute coronary artery syndromes induced increase in myocardial injury even increase of the mortality of the patients. After comparing the reported laboratory studies showing the cardioprotective effects and the clinical observations presenting the harmful consequences, we query whether the timing of the morphine treatment makes the difference in the prognosis of the ischemic/infarct myocardium. We found that intravenous injections of morphine (0.3 mg/kg) at 15 min before the acute myocardial ischemia, at 5 min and 20 min or 60 min after ligation of the coronary artery in separate groups of rats scheduled for acute myocardial ischemia, for 30 min or 90 min followed by reperfusion for 120 min, induced different results, reduction in the size of infarction, no effect and increases of the infarct sizes, respectively. The opioid µ- and kappa-receptors mediated the detrimental effect of morphine on the myocardial injury. The findings of this study suggest that administration of morphine may cause different consequences when used at different time in the pathology of acute myocardial ischemia and reperfusion. The underlying mechanisms in the pathology of acute myocardial ischemia warrant further study.

5.
J Evid Based Dent Pract ; 22(2): 101718, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35718428

RESUMO

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Joshi, Chaitanya; Bapat, Ranjeet; Anderson, William; Joshi, Chaitanya; Bapat, Ranjeet; Anderson, William; Dawson, Dana; Hijazi, Karolin; Cherukara, George (2021). "Detection of periodontal microorganisms in coronary atheromatous plaque specimens of myocardial infarction patients: A systematic review and meta-analysis." Trends in Cardiovascular Medicine 31(1): 69-82. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of data.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Boca/microbiologia , Placa Aterosclerótica/microbiologia , Doenças Cardiovasculares/microbiologia , Assistência Odontológica , Fatores de Risco de Doenças Cardíacas , Humanos , Placa Aterosclerótica/complicações , Fatores de Risco
6.
Cells ; 11(12)2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35741040

RESUMO

Myocardial infarction (MI), a type of coronary heart disease, has had a significantly increased incidence in recent years. The balance of cardiomyocyte apoptosis and autophagy after MI is one of the main determinants of patient prognosis. Both affect myocardial fibrosis and ventricular remodeling and regulate cell survival. However, there are few studies on the regulation mechanism of cardiomyocyte autophagy and apoptosis in the early stage after MI. In this study, based on analyzing the scRNA-seq and mRNA-seq data of mice in the early stage of MI, we found that the expression of S100a8 and S100a9 increased first and then decreased in the early stage of MI, and their expression level changed with the number of neutrophils. Further, through the functional enrichment analysis of the differentially expressed genes, we found that S100a8 and S100a9 were simultaneously associated with autophagy and apoptosis and could regulate autophagy and apoptosis of cardiomyocytes through MAPK or PI3K-AKT signaling pathways. This study provides valuable insights for clarifying the pathogenesis of early stage MI and improving its early treatment.


Assuntos
Infarto do Miocárdio , Proteínas Proto-Oncogênicas c-akt , Animais , Apoptose/genética , Autofagia , Humanos , Camundongos , Infarto do Miocárdio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
7.
Open Heart ; 9(1)2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35750420

RESUMO

OBJECTIVE: Short-term ambient fine particulate matter (PM2.5) is associated with adverse cardiovascular events including myocardial infarction (MI). However, few studies have examined associations between PM2.5 and subclinical cardiomyocyte damage outside of overt cardiovascular events. Here we evaluate the impact of daily PM2.5 on cardiac troponin I, a cardiomyocyte specific biomarker of cellular damage. METHODS: We conducted a retrospective cohort study of 2924 patients identified using electronic health records from the University of North Carolina Healthcare System who had a recorded MI between 2004 and 2016. Troponin I measurements were available from 2014 to 2016, and were required to be at least 1 week away from a clinically diagnosed MI. Daily ambient PM2.5 concentrations were estimated at 1 km resolution and assigned to patient residence. Associations between log-transformed troponin I and daily PM2.5 were evaluated using distributed lag linear mixed effects models adjusted for patient demographics, socioeconomic status and meteorology. RESULTS: A 10 µg/m3 elevation in PM2.5 3 days before troponin I measurement was associated with 0.06 ng/mL higher troponin I (95% CI=0.004 to 0.12). In stratified models, this association was strongest in patients that were men, white and living in less urban areas. Similar associations were observed when using 2-day rolling averages and were consistently strongest when using the average exposure over the 5 days prior to troponin I measurement. CONCLUSIONS: Daily elevations in PM2.5 were associated with damage to cardiomyocytes, outside of the occurrence of an MI. Poor air quality may cause persistent damage to the cardiovascular system leading to increased risk of cardiovascular disease and adverse cardiovascular events.


Assuntos
Poluentes Atmosféricos , Infarto do Miocárdio , Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Miócitos Cardíacos , North Carolina/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise , Estudos Retrospectivos , Sobreviventes , Troponina I
8.
BMC Cardiovasc Disord ; 22(1): 290, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35752771

RESUMO

BACKGROUND: This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI). METHODS: In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time. RESULTS: AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively. CONCLUSION: Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Trombocitopenia , Anticoagulantes/efeitos adversos , Antitrombinas/efeitos adversos , China/epidemiologia , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Hirudinas/efeitos adversos , Humanos , Fragmentos de Peptídeos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Trombocitopenia/induzido quimicamente , Resultado do Tratamento
9.
Int J Public Health ; 67: 1604319, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755955

RESUMO

Objectives: We evaluate the impact of the COVID-19 pandemic on unplanned hospitalization rates for patients without COVID-19, including their length of stay, and in-hospital mortality, overall, and for acute myocardial infarction (AMI), stroke, and heart failure in the Tuscany region of Italy. Methods: We carried out a population-based controlled interrupted time series study using segmented linear regression with an autoregressive error term based on admissions data from all public hospitals in Tuscany. The primary outcome measure was weekly hospitalization rates; secondary outcomes included length of stay, and in-hospital mortality. Results: The implementation of the pandemic-related mitigation measures and fear of infection was associated with large decreases in inpatient hospitalization rates overall (-182 [-234, -130]), unplanned hospitalization (-39 [-51, -26]), and for AMI (-1.32 [-1.98, -0.66]), stroke (-1.51 [-2.56, -0.44]), and heart failure (-8.7 [-11.1, -6.3]). Average length of stay and percent in-hospital mortality for select acute medical conditions did not change significantly. Conclusion: In Tuscany, Italy, the COVID-19 pandemic was associated with large reductions in hospitalization rates overall, as well as for heart failure, and the time sensitive conditions of AMI and stroke during the months January to July 2020.


Assuntos
COVID-19 , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , COVID-19/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Análise de Séries Temporais Interrompida , Infarto do Miocárdio/epidemiologia , Pandemias , Acidente Vascular Cerebral/epidemiologia
10.
Front Public Health ; 10: 894129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757636

RESUMO

Acute myocardial infarction (AMI) has a high mortality. The single-cell RNA sequencing (scRNA-seq) method was used to analyze disease heterogeneity at the single-cell level. From the Gene Expression Omnibus (GEO) database (GSE180678), AMI scRNA-seq were downloaded and preprocessed by the Seurat package. Gene expression data came from GSE182923. Cell cluster analysis was conducted. Cell types were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on hub genes. Drugs were predicted by protein-protein interaction (PPI) and molecular docking. In total, 7 cell clusters were defined based on the scRNA-seq dataset, and the clusters were labeled as 5 cell types by marker genes. Hematopoietic stem cell types as a differential subgroups were higher in AMI than in healthy tissues. From available databases and PPI analysis, 52 common genets were identified. Based on 52 genes, 5 clusters were obtained using the MCODE algorithm, and genes in these 5 clusters involved in immune and inflammatory pathways were determined. Correlation analysis showed that hematopoietic stem cell types were negatively correlated with ATM, CARM1, and CASP8 but positively correlated with CASP3 and PPARG. This was reversed with immune cells. Molecular docking analysis showed that DB05490 had the lowest docking score with PPARG. We identified 5 hub genes (ATM, CARM1, CASP8, CASP3, and PPARG) involved in AMI progression. Compound DB05490 was a potential inhibitor of PPAG.


Assuntos
Infarto do Miocárdio , Mapas de Interação de Proteínas , Caspase 3/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Humanos , Simulação de Acoplamento Molecular , Infarto do Miocárdio/genética , PPAR gama/genética , Mapas de Interação de Proteínas/genética , Análise de Sequência de RNA
11.
Rev Med Inst Mex Seguro Soc ; 60(2): 142-148, 2022 Mar 01.
Artigo em Espanhol | MEDLINE | ID: mdl-35758939

RESUMO

Background: The myocardial infarction-associated (MI) mortality is not only due cardiovascular complications, but intrahospital non-cardiovascular complications (IHnCVCs). The leuko-glycemic index (LGI) has been used as a prognostic marker for the development of cardiovascular complications in MI. We focused this study on identifying the cut-off point of LGI for the IHnCVCs development in patients with ST-segment elevation myocardial infarction (STEMI). Material and methods: In this single-center and crosssectional design, we included patients with STEMI. The biochemical analysis included glucose and leucocytes; with them we calculated the LGI. Receiver operating characteristic curve, univariate and bivariate analysis, and multivariate analysis for IHnCVCs development were performed. A p < 0.05 was considered statistically significant. Results: We included 1294 patients, 79.8% were men and 20.2% women. The main comorbidities were hypertension, diabetes mellitus and dyslipidemia. Six hundred forty-four (49.8%) patients presented IHNCVCs. The LGI > 1200 (AUC 0.817) predict the IHNCVCs development in STEMI patients. The variables that increased the IHNCVCs development were LGI > 1200, creatinine > 0.91 mg/dL, diabetes mellitus and age > 65 years. Hospital acquired pneumonia and cardiovascular complications increase the risk of death among STEMI patients. Conclusion: A LGI > 1200 increased, just over nine times, the risk of IHnCVC development in STEMI patients.


Introducción: la mortalidad asociada a infarto del miocardio (IM) no solo se debe a complicaciones cardiovasculares, sino tambien a complicaciones intrahospitalarias no cardiovasculares (CIHNC). El índice leuco-glucémico (ILG) se ha utilizado como un marcador pronóstico para el desarrollo de complicaciones cardiovasculares en el IM. Centramos este estudio en identificar el punto de corte de ILG para el desarrollo de CIHNC en pacientes con infarto de miocardio con elevación del segmento ST (IAMCEST). Material y métodos: en este diseño de un solo centro y transversal, incluimos pacientes con IAMCEST. El análisis bioquímico incluyó glucosa y leucocitos; se calculó ILG. Se realizaron análisis univariados y bivariados, curva ROC y análisis multivariado para el desarrollo de IAMCEST. Resultados: incluimos 1294 pacientes, 79.8% hombres y 20.2% mujeres. Las principales comorbilidades fueron: hipertensión arterial sistémica, diabetes mellitus y dislipidemia. Seiscientos cuarenta y cuatro pacientes (49.8%) presentaron CIHNC. El ILG > 1200 con área bajo la curva (AUC) 0.817 predice el desarrollo de CIHNC en pacientes con IAMCEST. Las variables que aumentaron el desarrollo de CIHNC fueron: ILG > 1200, creatinina > 0.91 mg/dL, diabetes mellitus y edad > 65 años. La neumonía intrahospitalaria y las complicaciones cardiovasculares aumentaron el riesgo de muerte entre los pacientes con IAMCEST. Conclusión: un LGI > 1200 aumentó más de nueve veces el riesgo de desarrollo de CIHNC en pacientes con IAMCEST.

12.
Redox Biol ; 54: 102370, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35759945

RESUMO

Red blood cells (RBCs) were shown to transport and release nitric oxide (NO) bioactivity and carry an endothelial NO synthase (eNOS). However, the pathophysiological significance of RBC eNOS for cardioprotection in vivo is unknown. Here we aimed to analyze the role of RBC eNOS in the regulation of coronary blood flow, cardiac performance, and acute myocardial infarction (AMI) in vivo. To specifically distinguish the role of RBC eNOS from the endothelial cell (EC) eNOS, we generated RBC- and EC-specific knock-out (KO) and knock-in (KI) mice by Cre-induced inactivation or reactivation of eNOS. We found that RBC eNOS KO mice had fully preserved coronary dilatory responses and LV function. Instead, EC eNOS KO mice had a decreased coronary flow response in isolated perfused hearts and an increased LV developed pressure in response to elevated arterial pressure, while stroke volume was preserved. Interestingly, RBC eNOS KO showed a significantly increased infarct size and aggravated LV dysfunction with decreased stroke volume and cardiac output. This is consistent with reduced NO bioavailability and oxygen delivery capacity in RBC eNOS KOs. Crucially, RBC eNOS KI mice had decreased infarct size and preserved LV function after AMI. In contrast, EC eNOS KO and EC eNOS KI had no differences in infarct size or LV dysfunction after AMI, as compared to the controls. These data demonstrate that EC eNOS controls coronary vasodilator function, but does not directly affect infarct size, while RBC eNOS limits infarct size in AMI. Therefore, RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.

13.
Curr Probl Cardiol ; : 101300, 2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35760149

RESUMO

The clinical presentation of acute coronary syndromes (ACS) as ST-elevation ACS (STEACS) or non-ST-elevation ACS (NSTEACS) differs between women and men. The aim of this study was to describe the difference in the clinical presentation of ACS between sexes. A total of 10,019 patients included in the Epi-Cardio Registry were analyzed. A higher proportion of women than men presented with NSTEACS (60.3% vs. 46.7%; p <0.001). The difference between sexes was driven by a higher prevalence of ACS with non-obstructive coronary arteries (20.9% vs. 6.6%) mainly in young women, since ACS without coronary lesions were mostly NSTEACS (77.7% vs. 22.3%). In patients with obstructive coronary heart disease, there were no differences in the clinical presentation between sexes. In conclusion, younger women are more likely than men to present ACS with non-obstructive coronary arteries, whereas no significant difference exists between sexes regarding the prevalence of ACS with obstructive coronary artery disease.

14.
J Neurochem ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35762284

RESUMO

The relevance between circulating metabolites and vascular events remains controversial and comprehensive studies are lacking. We sought to investigate the prospective associations of plasma metabolomics with risks of incident stroke, ischemic stroke (IS), hemorrhagic stroke (HS) and myocardial infarction (MI). Within the UK Biobank cohort, 249 circulating metabolites were measured in 90,438 participants without baseline vascular diseases. Cox proportional hazards regressions were applied to estimate adjusted hazard ratios (HRs) for per 1 standard deviation increment in metabolites. The least absolute shrinkage and selection operator algorithm was used for selecting metabolite subsets. During a median of 9.0 years of follow-up, we documented 833 incident stroke and 1,256 MI cases. Lipid constituents, comprising cholesterol, cholesteryl esters, free cholesterol, phospholipids, and total lipids, in very low- (VLDL), intermediate- (IDL), and low-density lipoprotein (LDL) particles were positively associated with MI risk (HR=1.12 to 1.36; 95% CI=1.06 to 1.44), while in high-density lipoprotein (HDL) particles showed inverse associations (HR=0.68 to 0.81; 95% CI=0.63 to 0.87). Similar association pattern with MI was also observed for VLDL, IDL, LDL, and HDL particles themselves. In contrast, triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI risk (HR=1.14 to 1.28; 95% CI=1.08 to 1.35) and, to a slightly lesser extent, with stroke and IS. Unsaturation of fatty acids and albumin were inversely associated with risks of stroke, IS and MI. In contrast, the linear association for HS is absent. When combining multiple metabolites, the metabolite risk score captured a drastically elevated risk of all vascular events, about twice that of any single metabolite. Taken together, circulating metabolites showed remarkably widespread associations with incident MI, but substantially weakened associations with risks of stroke and its subtypes. Exhaustive metabolomics profiling may shed light on vascular risk prediction and, in turn, guide pertinent strategies of intervention and treatment.

15.
DNA Cell Biol ; 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35763313

RESUMO

Plasma cell-free DNA (cfDNA) was elevated in patients with acute myocardial infarction (AMI) or heart failure (HF). However, whether cfDNA could serve as a predictor for risk of HF after AMI remains unknown. In this study, we conducted a pilot prospective cohort study in which 98 AMI patients were enrolled from a single center to assess the association between cfDNA levels at admission and risk of HF in an AMI population. Patients with cfDNA above the median level (14.39 ng/mL) showed higher low-density lipoprotein cholesterol, cardiac troponin I (cTnI), and soluble suppression of tumorigenicity 2 (sST2) levels compared with patients below the median. cfDNA was positively correlated with cTnI (r = 0.377, p < 0.001) and sST2 (r = 0.443, p < 0.001). Within a median follow-up of about 345 days, 46 patients (52.6%) developed HF. Multivariate Cox analysis showed that a higher cfDNA (above the cutoff value: 9.227 ng/mL) was an effective risk predictor (C-index = 0.74, 95% confidence interval [CI]: 0.733-0.748) for HF incidence after AMI (adjusted hazard ratio [HR]: 2.805; 95% CI: 1.087-7.242; p = 0.033). Moreover, a linear association was observed between cfDNA and risk of HF incidence adjusted for by age, gender, and history of chronic kidney disease (p for linear trend = 0.044). Taken together, the cfDNA levels at admission are associated with the incidence of HF in AMI patients. A positive correlation between cfDNA and the fibrotic factor sST2 was proved, but the underlying mechanisms require further study.

16.
J Vasc Surg ; 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35667605

RESUMO

BACKGROUND: Major adverse cardiac events (MACEs) are the primary cause of death after carotid endarterectomy (CEA). We sought to determine whether selective coronary revascularization of CEA patients with asymptomatic coronary ischemia can reduce the risk of MACEs, myocardial infarction (MI), and cardiac death after endarterectomy compared with CEA patients receiving standard cardiac evaluation and care. METHODS: Two groups of patients with no cardiac history or symptoms undergoing elective CEA were compared. Group I: patients enrolled in a prospective study of noninvasive preoperative cardiac evaluation using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) to detect asymptomatic (silent) coronary ischemia with selective postoperative coronary revascularization. Group II: matched Control patients with standard preoperative cardiac evaluation and no postoperative coronary revascularization. Lesion-specific coronary ischemia in group I was defined as FFRCT ≤ 0.80 distal to coronary stenosis with severe ischemia defined as FFRCT ≤ 0.75. End points included MACEs, cardiac death, MI, cardiovascular (CV) death, stroke, and all-cause death through 3-year follow-up. RESULTS: Group I (n = 100) and group II (n = 100) patients were similar in age (68 vs 67 years), gender (65% vs 62% male), comorbidities, and indications for CEA (53% vs 48% symptomatic carotid stenosis). In group I, FFRCT analysis revealed lesion-specific coronary ischemia in 57% of patients, severe coronary ischemia in 44%, left main ischemia in 7%, and multivessel ischemia in 28%. The status of coronary ischemia in group II was unknown. CEA was performed without complications in both groups, and all patients received optimal postoperative medical therapy. In group I, elective coronary revascularization was performed in 33 patients (27 percutaneous coronary intervention; 6 coronary artery bypass grafting) 1 to 3 months after CEA. Group II patients had no elective coronary revascularization. During 3-year follow-up, compared with group II, group I patients had fewer MACEs (4% vs 17%, hazard ratio [HR]: 0.21 [95% confidence interval (CI): 0.07-0.63], P = .004), fewer cardiac deaths (2% vs 9%, HR: 0.20 [95% CI: 0.04-0.95], P = .030), fewer MIs (3% vs 17%, HR: 0.16 [95% CI: 0.05-0.54], P = .001), and fewer CV deaths (2% vs 12%, HR: 0.16 [95% CI: 0.004-0.07], P = .009). There were no significant differences in the rates of stroke or all-cause death. CONCLUSIONS: Preoperative diagnosis of silent coronary ischemia with selective coronary revascularization after CEA may reduce the risk of MACEs, cardiac death, MI, and CV death during 3-year follow-up compared with CEA patients receiving standard cardiac evaluation and care.

17.
Cells ; 11(11)2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35681549

RESUMO

p66Shc is a widely expressed protein that governs a variety of cardiovascular pathologies by generating, and exacerbating, pro-apoptotic ROS signals. Here, we review p66Shc's connections to reactive oxygen species, expression, localization, and discuss p66Shc signaling and mitochondrial functions. Emphasis is placed on recent p66Shc mitochondrial function discoveries including structure/function relationships, ROS identity and regulation, mechanistic insights, and how p66Shc-cyt c interactions can influence p66Shc mitochondrial function. Based on recent findings, a new p66Shc mitochondrial function model is also put forth wherein p66Shc acts as a rheostat that can promote or antagonize apoptosis. A discussion of how the revised p66Shc model fits previous findings in p66Shc-mediated cardiovascular pathology follows.


Assuntos
Mitocôndrias , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Adaptadoras da Sinalização Shc/metabolismo , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo
18.
J Am Heart Assoc ; 11(12): e024330, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35699193

RESUMO

Background Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)-secreted EVs-derived miR-200b-3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl-2-like protein 11) . Methods and Results EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR-200b-3p for overexpression were injected into MI mice. The effect of miR-200b-3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR-200b-3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR-200b-3p on MI mice. EVs from MSCs were successfully extracted. MSCs-EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR-200b-3p further enhanced the effects of MSCs-EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR-200b-3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR-200b-3p-modified MSCs-EVs in MI mice. Conclusions A summary was obtained that miR-200b-3p-encapsulated MSCs-EVs protect against MI-induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.


Assuntos
Vesículas Extracelulares , Células-Tronco Mesenquimais , MicroRNAs , Infarto do Miocárdio , Animais , Apoptose , Proteína 11 Semelhante a Bcl-2/metabolismo , Vesículas Extracelulares/metabolismo , Fibrose , Inflamação/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/terapia
19.
BMJ Open ; 12(6): e062702, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35760536

RESUMO

INTRODUCTION: Inflammation is emerging as an important risk factor for atherosclerotic cardiovascular disease and has been a recent target for many novel therapeutic agents. However, comparative evidence regarding efficacy of these anti-inflammatory treatment options is currently lacking. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials evaluating the effect of anti-inflammatory agents on cardiovascular outcomes in patients with known cardiovascular disease. Studies will be retrieved from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC and conference abstract handsearching. No publication date or language restrictions will be imposed. Eligible interventions must have some component of anti-inflammatory agent. These include (but are not limited to): non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, prednisone, methotrexate, canakinumab, pexelizumab, anakinra, succinobucol, losmapimod, inclacumab, atreleuton, LP-PLA2 (darapladib) and sPLA2 (varespladib). The primary outcomes will include major adverse cardiac events (MACE), and each individual component of MACE (myocardial infarction, stroke and cardiovascular death). Key secondary outcomes will include unstable angina, heart failure, all-cause mortality, cardiac arrest and revascularisation. Screening, inclusion, data extraction and quality assessment will be performed independently by two reviewers. Network meta-analysis based on the random effects model will be conducted to compare treatment effects both directly and indirectly. The quality of the evidence will be assessed with appropriate tools including the Grading of Recommendations, Assessment, Development and Evaluation profiler or Confidence in Network Meta-Analysis tool. ETHICS AND DISSEMINATION: Ethics approval is not required for this systematic review. The findings will be disseminated through a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022303289.

20.
Subst Abuse Treat Prev Policy ; 17(1): 48, 2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35761409

RESUMO

BACKGROUND: According to the World Drug Report, cocaine is the second most used drug globally after cannabis. Online discussion forums enable the understanding of authentic drug users' experience as it is anonymous. Therefore, this study determined the uses, effects and toxicity of cocaine from the perspectives' of e-psychonauts. METHODS: A qualitative study was conducted using six popular discussion forums. From these discussion forums, 1229 posts from 50 threads were subject to thematic analysis. Hence, the information from these threads were examined carefully for patterns and codes among the data. The codes were then collated into subthemes and themes. RESULTS: The four main themes emerging from the study were related to cocaine characteristics and use, e-psychonauts' knowledge and experience, desired effects and adverse events. The main characteristic associated with cocaine use was purity that was highest in the US being nearest to the source. The most common cutting agent encountered in cocaine samples was levamisole that increased the chances of immunosuppression and cardiovascular toxicity. Purity depended on the source of purchase that included street dealers, dark web and surface web. Hence, e-psychonauts recommended purchase of cocaine from known dealers rather than websites with unknown sources. E-psychonauts mainly used cocaine in social context and parties or to self-medicate against anxiety and depression. Effects desired from cocaine use were mainly euphoria and increased energy. However, tachycardia and myocardial infarction were the main adverse events. It is noteworthy to mention that myocardial infarction was idiosyncratic and was often lethal. Myocardial infarction was more often reported when cocaine was combined with alcohol due to the production of cocaethylene. Social harm was also reported as a consequence for the use of cocaine that resulted in homelessness and broken relationships. CONCLUSION: Online discussion forums allowed the understanding of e-psychonauts' experience with cocaine use. Not only it informed about the sources and modalities of use of cocaine but also about the adverse events and social harm associated with cocaine use. The present findings serve as useful information for practitioners and healthcare professionals dealing with cocaine users.

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