RESUMO
Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.
Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Infarto do Miocárdio , Nanopartículas , Infarto do Miocárdio/terapia , Animais , Nanopartículas/química , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Recuperação de Função Fisiológica , Transplante de Células-Tronco Mesenquimais/métodos , Humanos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos , Microbolhas , Ondas UltrassônicasRESUMO
Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that â¼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.
Assuntos
Proliferação de Células , MicroRNAs , Infarto do Miocárdio , Miócitos Cardíacos , Estresse Oxidativo , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Suínos , Hidrogéis/química , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction. METHODS: DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality. RESULTS: After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study. CONCLUSION: Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259-8105.
Assuntos
LDL-Colesterol , Infarto do Miocárdio , Nozes , Humanos , Masculino , Feminino , LDL-Colesterol/sangue , Pessoa de Meia-Idade , Brasil , Dieta/métodos , Dieta/estatística & dados numéricos , Adulto , IdosoRESUMO
Objective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI. Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC). Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy. Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.
Assuntos
Fragilidade , Infarto do Miocárdio , Curva ROC , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Feminino , Idoso , Estudos Retrospectivos , Fragilidade/diagnóstico , Prognóstico , Pessoa de Meia-Idade , Medição de Risco/métodos , Fatores de Risco , Neutrófilos , Idoso de 80 Anos ou mais , China , Modelos Logísticos , Ácido Láctico/sangueRESUMO
BACKGROUND: Silent myocardial infarction (SMI) frequently goes undetected, yet it is associated with increased cardiovascular morbidity and mortality. The impact of intensive systolic blood pressure (SBP) lowering on the risk of SMI in those with hypertension remains uncertain. METHODS: In this post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), participants with serial electrocardiograms (ECGs) during the trial were included. SPRINT investigated the benefit of intensive SBP lowering, aiming for < 120 mmHg compared to the standard SBP goal of < 140 mmHg. Incident SMI was defined as evidence of new MI on an ECG without adjudicated recognized myocardial infarction (RMI). RESULTS: During a median follow-up of 3.9 years, a total of 234 MI events (55 SMI and 179 RMI) occurred. Intensive, compared to standard, SBP lowering resulted in a lower rate of SMI (incidence rate 1.1 vs. 2.3 cases per 1000 person-years, respectively; HR [95% CI]: 0.48 [0.27-0.84]). Similarly, intensive, compared to standard, BP lowering reduced the risk of RMI (incidence rate 4.6 vs. 6.5 cases per 1000 person-years, respectively; HR [95% CI]: 0.71 [0.52-0.95]). No significant differences were noted between the strength of the association of intensive BP control on lowering the risk of SMI and RMI (p-value for HR differences = 0.23). CONCLUSIONS: This study shows that in adults with hypertension, the benefits of intensive SBP lowering, compared with standard BP lowering, go beyond the prevention of RMI to include the prevention of SMI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.
Assuntos
Anti-Hipertensivos , Eletrocardiografia , Hipertensão , Infarto do Miocárdio , Humanos , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/complicações , Masculino , Feminino , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Anti-Hipertensivos/uso terapêutico , Eletrocardiografia/métodos , Pessoa de Meia-Idade , Idoso , Incidência , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Seguimentos , Fatores de RiscoRESUMO
Left ventricular pseudoaneurysm is a serious and rare disorder that usually develops after acute myocardial infarction. It can lead to potentially lethal mechanical complications, such as acute left ventricular free wall rupture. This report presents the case of a 64-year-old man with a left ventricular pseudoaneurysm and myocardial rupture that was managed by left ventricular restoration with aneurysmectomy and coronary artery bypass with 2 grafts.
Assuntos
Falso Aneurisma , Ponte de Artéria Coronária , Aneurisma Cardíaco , Ventrículos do Coração , Humanos , Masculino , Falso Aneurisma/cirurgia , Falso Aneurisma/etiologia , Falso Aneurisma/diagnóstico , Pessoa de Meia-Idade , Ventrículos do Coração/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Aneurisma Cardíaco/cirurgia , Aneurisma Cardíaco/etiologia , Aneurisma Cardíaco/diagnóstico , Ponte de Artéria Coronária/métodos , Angiografia Coronária , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Procedimentos Cirúrgicos Cardíacos/métodos , Resultado do Tratamento , Ruptura Cardíaca Pós-Infarto/cirurgia , Ruptura Cardíaca Pós-Infarto/etiologia , Ruptura Cardíaca Pós-Infarto/diagnósticoRESUMO
Neutrophils are critical mediators of both the initiation and resolution of inflammation after myocardial infarction (MI). Overexuberant neutrophil signaling after MI exacerbates cardiomyocyte apoptosis and cardiac remodeling while neutrophil apoptosis at the injury site promotes macrophage polarization toward a pro-resolving phenotype. Here, we describe a nanoparticle that provides spatiotemporal control over neutrophil fate to both stymie MI pathogenesis and promote healing. Intravenous injection of roscovitine/catalase-loaded poly(lactic-co-glycolic acid) nanoparticles after MI leads to nanoparticle uptake by circulating neutrophils migrating to the infarcted heart. Activated neutrophils at the infarcted heart generate reactive oxygen species, triggering intracellular release of roscovitine, a cyclin-dependent kinase inhibitor, from the nanoparticles, thereby inducing neutrophil apoptosis. Timely apoptosis of activated neutrophils at the infarcted heart limits neutrophil-driven inflammation, promotes macrophage polarization toward a pro-resolving phenotype, and preserves heart function. Modulating neutrophil fate to tune both inflammatory and reparatory processes may be an effective strategy to treat MI.
Assuntos
Apoptose , Inflamação , Macrófagos , Infarto do Miocárdio , Nanopartículas , Neutrófilos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Roscovitina , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/tratamento farmacológico , Animais , Neutrófilos/imunologia , Neutrófilos/metabolismo , Inflamação/patologia , Nanopartículas/química , Apoptose/efeitos dos fármacos , Roscovitina/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Masculino , Ácido Poliglicólico/química , Ácido Láctico/metabolismo , Modelos Animais de Doenças , HumanosRESUMO
BACKGROUND: Dyslipidemia is prominently associated with adverse outcomes in patients with coronary artery disease (CAD). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel comprehensive lipid index. However, limited evidence exists on the relationship of the NHHR with the risk of adverse outcomes in patients with CAD. This study aimed to explore the associations between the NHHR and adverse outcomes and identify the optimal NHHR ranges linked to the lowest adverse outcome risk in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Among 2253 patients with CAD undergoing PCI, 2251 with available total cholesterol and HDL-C levels were analyzed. Furthermore, all patients were classified into quintiles based on the NHHR. The primary outcome was the incidence of MACCEs, comprising cardiac mortality, acute myocardial infarction, stroke, and repeat revascularization. Multivariable logistic regression analysis was used to assess the relationship between the NHHR and MACCEs. Moreover, restricted cubic spline (RCS) analysis was performed to quantify nonlinearity. Lastly, the consistency between these associations was confirmed by conducting subgroup and interaction analyses. RESULTS: A total of 270 patients experienced MACCEs over a median follow-up of 29.8 months (interquartile range, 25.6-34 months). After adjustment for confounding variables, the adjusted ORs (95% CIs) of the patients in quintiles 2, 3, 4, and 5 were 0.79 (0.52-1.20), 0.64 (0.42-0.99), 1.00 (0.67-1.48), and 1.17 (0.74-1.64), respectively (reference group: quintile 1). Additionally, RCS analysis demonstrated a U-shaped relationship between the NHHR and MACCEs, with an inflection point at an NHHR of 3.119 using a two-piecewise regression model. This relationship was consistent across the various subgroups, while significant interactions were not observed in these associations.The ORs and 95% CIs to the left and right of the inflection point were 0.734 (0.551-0.978) and 1.231 (1.038-1.460), respectively. CONCLUSIONS: This study reveals a U-shaped association between baseline NHHR and MACCE incidence in patients with CAD undergoing PCI.
Assuntos
HDL-Colesterol , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Masculino , Feminino , HDL-Colesterol/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Fatores de Risco , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , LDL-Colesterol/sangue , Colesterol/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Acute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI. OBJECTIVE: The purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI). METHODS: The clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE. RESULTS: Compared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE. CONCLUSION: This study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI.
Assuntos
MicroRNAs , Infarto do Miocárdio , Intervenção Coronária Percutânea , RNA Longo não Codificante , Humanos , Masculino , Feminino , MicroRNAs/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , RNA Longo não Codificante/sangue , Prognóstico , Idoso , Biomarcadores/sangueRESUMO
BACKGROUND: MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI). Percutaneous coronary intervention (PCI) is currently the most direct and effective procedure to treat AMI, but the occurrence of postoperative cardiovascular events (MACE) affects patients' quality of life. The objective of this study was to identify a new biomarker that could provide a theoretical basis for the prevention of MACE in patients with AMI undergoing PCI. METHODS: 142 AMI patients who underwent PCI and 130 healthy volunteers were selected as study subjects. Detection of miR-636 expression level by fluorescence quantitative PCR. ROC, Kaplan-Meier and Cox regression analyses were applied to evaluate the diagnostic and prognostic value of miR-636 for AMI. The miR-636 target genes were predicted and enriched for GO function and KEGG pathway. RESULTS: MiR-636 expression levels were elevated in patients with AMI. ROC curve analysis showed that miR-636 had a feasible diagnostic value in distinguishing AMI patients from healthy controls miR-636 expression levels were elevated in patients who developed MACEs. ROC results showed that miR-636 had significant diagnostic value in differentiating AMI patients with and without MACEs after PCI treatment. GO and KEGG enrichment analyses showed that miR-636 may transmit information to vesicles formed by the cell membrane. CONCLUSIONS: MiR-636 expression serves as a biomarker for diagnosing AMI and predicting the occurrence of MACE after PCI.
Assuntos
Biologia Computacional , MicroRNAs , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , MicroRNAs/genética , Masculino , Feminino , Infarto do Miocárdio/genética , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/diagnóstico , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Biomarcadores/sangue , Idoso , Valor Preditivo dos Testes , Prognóstico , Curva ROCRESUMO
OBJECTIVES: Post-myocardial infarction ventricular septal rupture (PIVSR) is one of the most severe types of mechanical complications after acute myocardial infarction (AMI) with high mortality and poor prognosis. The risk factors for short-term mortality of patients with PIVSR may be not widely recognized. We aimed to assess the prevalence and short-term mortality risk predictors of PIVSR. METHODS: A total of 62 patients with a diagnosis of PIVSR were admitted to three top general public hospitals in Chongqing, China. Clinical characteristics and short-term outcomes of patients with PIVSR were compared. Predictors of PIVSR were assessed using logistic regression analysis. RESULTS: Mean age was 70.7 ± 10.7 years (38.7% female). The overall in-hospital mortality of PIVSR remained high (71%). Most (47/62) of the patients were in Killip class III or IV at the time of rupture diagnosis. Logistic regression analysis revealed that white blood cell count (WBC, OR 1.619, 95% CI 1.172-2.237, P = 0.005), cardiogenic shock (OR 47.706, 95%CI 2.859-795.945, P = 0.007) and left ventricular ejection fraction (LVEF, OR 0.803, 95%CI 0.689-0.936, P = 0.009) were independent risk factors of in-hospital early mortality. The nomogram developed for predicting the risk of short-term mortality showed a robust discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.956 (95%CI 0.912-1.000). CONCLUSION: The short-term mortality of PIVSR remained high. WBC, cardiogenic shock, and LVEF were the independent predictive factors of short-term mortality. Our nomogram might be used to predict early mortality of patients with PIVSR.
Assuntos
Mortalidade Hospitalar , Infarto do Miocárdio , Ruptura do Septo Ventricular , Humanos , Feminino , Masculino , Ruptura do Septo Ventricular/etiologia , Estudos Retrospectivos , Idoso , Fatores de Risco , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Pessoa de Meia-Idade , China/epidemiologia , Prognóstico , Idoso de 80 Anos ou mais , Choque Cardiogênico/etiologia , Choque Cardiogênico/mortalidade , Fatores de TempoRESUMO
This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke.
Assuntos
LDL-Colesterol , Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Humanos , Masculino , Feminino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/tratamento farmacológico , LDL-Colesterol/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Idoso de 80 Anos ou mais , Lipídeos/sangue , Sistema de Registros , Infarto do Miocárdio/sangue , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: Myocardial ischemia-reperfusion injury (MI/RI) is an unavoidable risk event for acute myocardial infarction, with ferroptosis showing close involvement. We investigated the mechanism of MI/RI inducing myocardial injury by inhibiting the ferroptosis-related SLC7A11/glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway and activating mitophagy. METHODS: A rat MI/RI model was established, with myocardial infarction area and injury assessed by TTC and H&E staining. Rat cardiomyocytes H9C2 were cultured in vitro, followed by hypoxia/reoxygenation (H/R) modeling and the ferroptosis inhibitor lipoxstatin-1 (Lip-1) treatment, or 3-Methyladenine or rapamycin treatment and overexpression plasmid (oe-SLC7A11) transfection during modeling. Cell viability and death were evaluated by CCK-8 and LDH assays. Mitochondrial morphology was observed by transmission electron microscopy. Mitochondrial membrane potential was detected by fluorescence dye JC-1. Levels of inflammatory factors, reactive oxygen species (ROS), Fe2+, malondialdehyde, lipid peroxidation, GPX4 enzyme activity, glutathione reductase, GSH and glutathione disulfide, and SLC7A11, GPX4, LC3II/I and p62 proteins were determined by ELISA kit, related indicator detection kits and Western blot. RESULTS: The ferroptosis-related SLC7A11/GSH/GPX4 pathway was repressed in MI/RI rat myocardial tissues, inducing myocardial injury. H/R affected GSH synthesis and inhibited GPX4 enzyme activity by down-regulating SLC7A11, thus promoting ferroptosis in cardiomyocytes, which was averted by Lip-1. SLC7A11 overexpression improved H/R-induced cardiomyocyte ferroptosis via the GSH/GPX4 pathway. H/R activated mitophagy in cardiomyocytes. Mitophagy inhibition reversed H/R-induced cellular ferroptosis. Mitophagy activation partially averted SLC7A11 overexpression-improved H/R-induced cardiomyocyte ferroptosis. H/R suppressed the ferroptosis-related SLC7A11/GSH/GPX4 pathway by inducing mitophagy, leading to cardiomyocyte injury. CONCLUSIONS: Increased ROS under H/R conditions triggered cardiomyocyte injury by inducing mitophagy to suppress the ferroptosis-related SLC7A11/GSH/GPX4 signaling pathway activation.
Assuntos
Sistema y+ de Transporte de Aminoácidos , Modelos Animais de Doenças , Ferroptose , Glutationa , Mitofagia , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Ratos Sprague-Dawley , Transdução de Sinais , Ferroptose/efeitos dos fármacos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Glutationa/metabolismo , Masculino , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Linhagem Celular , Mitofagia/efeitos dos fármacos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/genética , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/efeitos dos fármacos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVES: We aimed to study the impact of gout as a correlative risk factor in the incidence of acute myocardial infarction (AMI) among patients without known MI risk factors. Our study population was obtained from the National Inpatient Sample (NIS) 2011-2018 using the International Classification of Diseases, Ninth and Tenth Revisions. METHODS: This study included patients without cardiovascular disease (CVD), and various outcomes were compared among patients with and without gout. Cohorts were weighted using an algorithm provided by the NIS, which allows for national estimates. Our primary endpoint was the odds of developing an MI, and secondary endpoints were adverse hospital events and length of stay. In total, 117,261,842 patients without CVD risk factors were included in this study, 187,619 (0.16%) of whom had a diagnosis of gout. RESULTS: Patients without CVD risk factors who had gout were older and more likely to be male compared with patients without gout. Among patients without CVD risk factors, the odds of having an AMI were significantly higher in those with gout compared with those without, even after adjusting for chronic nonsteroidal anti-inflammatory drug and oral steroid use. Moreover, patients without CVD risk factors and with gout were more likely to develop acute renal failure, acute thromboembolic event, shock, acute gastrointestinal bleed, and arrhythmia compared with those without gout. Furthermore, patients without CVD risk factors who were admitted with gout had higher mortality compared with those without gout. CONCLUSIONS: In our study, we found that patients without risk factors for AMI who had gout were more likely to develop AMI compared with those without gout. Furthermore, the same patients were more likely to develop other adverse outcomes. Even with proper management, these individuals should be monitored closely for coronary events.
Assuntos
Gota , Infarto do Miocárdio , Humanos , Gota/epidemiologia , Gota/complicações , Gota/diagnóstico , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estados Unidos/epidemiologia , Fatores de Risco , Incidência , Fatores de Risco de Doenças Cardíacas , AdultoRESUMO
BACKGROUND: In this study, we explored the impact of hypothyroidism and thyroid hormone replacement therapy on the risk of developing cardiovascular diseases, including myocardial infarction, heart failure, and cardiac death, via Mendelian randomization analysis. METHODS: Genetic instrumental variables related to hypothyroidism, levothyroxine treatment (refer to Participants were taking the medication levothyroxine sodium) and adverse cardiovascular events were obtained from a large publicly available genome-wide association study. Two-sample Mendelian randomization analysis was performed via inverse-variance weighting as the primary method. To ensure the reliability of our findings, we performed MRâEgger regression, Cochran's Q statistic, and leave-one-out analysis. Additionally, multivariable Mendelian randomization was employed to regulate confounding factors, including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), diabetes, cholesterol, low-density lipoprotein (LDL), triglycerides and metformin. A mediation analysis was conducted to assess the mediating effects on the association between exposure and outcome by treating atrial fibrillation and stroke as mediator variables of levothyroxine treatment and bradycardia as mediator variables of hypothyroidism. RESULTS: Genetically predicted hypothyroidism and levothyroxine treatment were significantly associated with the risk of experiencing myocardial infarction [levothyroxine: odds ratio (OR) 3.75, 95% confidence interval (CI): 1.80-7.80; hypothyroidism: OR: 15.11, 95% CI: 2.93-77.88]. Levothyroxine treatment was also significantly related to the risk of experiencing heart failure (OR: 2.16, 95% CI: 1.21-3.88). However, no associations were detected between hypothyroidism and the risk of experiencing heart failure or between hypothyroidism or levothyroxine treatment and the risk of experiencing cardiac death. After adjusting for confounding factors, the results remained stable. Additionally, mediation analysis indicated that atrial fibrillation and stroke may serve as potential mediators in the relationships between levothyroxine treatment and the risk of experiencing heart failure or myocardial infarction. CONCLUSION: The results of our study suggest a positive association between hypothyroidism and myocardial infarction and highlight the potential effects of levothyroxine treatment, the main thyroid hormone replacement therapy approach, on increasing the risk of experiencing myocardial infarction and heart failure.
Assuntos
Doenças Cardiovasculares , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hipotireoidismo , Análise da Randomização Mendeliana , Tiroxina , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/genética , Hipotireoidismo/epidemiologia , Tiroxina/uso terapêutico , Medição de Risco , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Terapia de Reposição Hormonal/efeitos adversos , Fatores de Risco , Fenótipo , Feminino , Infarto do Miocárdio/genética , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/diagnóstico , Polimorfismo de Nucleotídeo Único , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Masculino , Variantes Farmacogenômicos , Fatores de Risco de Doenças CardíacasRESUMO
BACKGROUND: In developing nations, myocardial infarction (MI) remains a significant contributor to deaths from sudden cardiac arrest, with diet playing a key role in its incidence through oxidative stress mechanisms. Although the connection between the Dietary Antioxidant Index (DAI) and cardiovascular diseases has been demonstrated in some studies, the relationship between DAI and MI has not been extensively explored. Therefore, this research aims to investigate this association. METHODS: We conducted a nested case-control study involving 156 MI cases and 312 healthy controls, utilizing data from the Fasa Adults Cohort Study (FACS), a population-based study of individuals aged 35-70 residing in Fasa, Iran, with 11,097 participants included at baseline. The DAI was determined by normalizing the intake values of six dietary vitamins and minerals, adjusting by subtracting the global mean, and then dividing by the global standard deviation. MI diagnosis was established by an experienced cardiologist using electronic medical records. Conditional logistic regression was employed to examine the association between DAI and MI. RESULTS: There were no significant differences between the case and control groups in terms of age (P = 0.96), gender distribution (P = 0.98), and education level (P = 0.38). In a multiple conditional logistic regression analysis, after adjusting for key variables-including body mass index (BMI), smoking status, education level, and serum levels of triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), fasting blood sugar (FBS), saturated fatty acids (SFA), and polyunsaturated fatty acids (PUFA)-an inverse association was found between DAI and the risk of myocardial infarction (MI) [adjusted Odds Ratio (Adj OR) = 0.88, 95% Confidence Interval (CI): 0.85-0.92; P < 0.001]. CONCLUSIONS: This study highlights the crucial role of the DAI in reducing the risk of myocardial infarction. Promoting diets rich in antioxidants presents a straightforward and effective strategy for MI prevention and the promotion of cardiovascular health, underscoring the novelty and significance of this research in dietary approaches to disease prevention.
Assuntos
Antioxidantes , Infarto do Miocárdio , Fatores de Proteção , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/sangue , Irã (Geográfico)/epidemiologia , Estudos de Casos e Controles , Idoso , Adulto , Antioxidantes/administração & dosagem , Medição de Risco , Dieta Saudável , Fatores de Risco , Valor Nutritivo , Comportamento de Redução do Risco , Recomendações NutricionaisRESUMO
BACKGROUND: Myocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations. RESULTS: We have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins. CONCLUSIONS: These findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.
Assuntos
Ácido Elágico , Ouro , Nanopartículas Metálicas , Infarto do Miocárdio , Estresse Oxidativo , Espécies Reativas de Oxigênio , Peixe-Zebra , Animais , Ouro/química , Nanopartículas Metálicas/química , Infarto do Miocárdio/tratamento farmacológico , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Ácido Elágico/farmacologia , Ácido Elágico/química , Estresse Oxidativo/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Acute myocardial infarction (AMI) is a serious, deadly disease with a high incidence. However, it remains unclear how necroptosis affects the pathophysiology of AMI. Using bioinformatic analyses, this study investigated necroptosis in AMI. METHODS: We obtained the GSE66360 dataset related to AMI by the GEO database. Venn diagrams were used to identify necroptosis-related differential genes (NRDEGs). The genes with differential expression in AMI were analyzed using gene set enrichment analysis, and a PPI network was established. A transcription factor prediction and enrichment analysis were conducted for the NRDEGs, and the relationships between AMI, NRDEGs, and immune cells were determined. Finally, in the additional dataset, NRDEG expression levels, immune infiltration, and ROC curve analysis were confirmed, and gene expression levels were further verified experimentally. RESULTS: GSEA revealed that necroptosis pathways were significantly enriched in AMI. We identified 10 NRDEGs, including TNF, TLR4, FTH1 and so on. Enrichment analysis indicated that the NOD-like receptor and NF-kappa B signaling pathways were significantly enriched. Four NRDEGs, FTH1, IFNGR1, STAT3, and TLR4, were identified; however, additional datasets and further experimental validation are required to confirm their roles. In addition, we determined that a high abundance of macrophages and neutrophils prompted AMI development. CONCLUSIONS: In this study, four potential genes that affect the development of AMI through necroptosis (FTH1, IFNGR1, STAT3, and TLR4) were identified. In addition, we found that a high abundance of macrophages and neutrophils affected AMI. This helps determine the pathological mechanism of necroptosis and immune cells that influence AMI and provides a novel strategy for targeted therapy.
Assuntos
Biologia Computacional , Infarto do Miocárdio , Necroptose , Infarto do Miocárdio/genética , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Humanos , Necroptose/genética , Necroptose/fisiologiaRESUMO
BACKGROUND: Regional Wall Motion Abnormality (RWMA) serves as an early indicator of myocardial infarction (MI), the global leader in mortality. Accurate and early detection of RWMA is vital for the successful treatment of MI. Current automated echocardiography analyses typically concentrate on peak values from left ventricular (LV) displacement curves, based on LV contour annotations or key frames during the heart's systolic or diastolic phases within a single echocardiographic cycle. This approach may overlook the rich motion field features available in multi-cycle cardiac data, which could enhance RWMA detection. METHODS: In this research, we put forward an innovative approach to detect RWMA by harnessing motion information across multiple echocardiographic cycles and multi-views. Our methodology synergizes U-Net-based segmentation with optical flow algorithms for detailed cardiac structure delineation, and Temporal Convolutional Networks (ConvNet) to extract nuanced motion features. We utilize a variety of machine learning and deep learning classifiers on both A2C and A4C views echocardiograms to enhance detection accuracy. A three-phase algorithm-originating from the HMC-QU dataset-incorporates U-Net for segmentation, followed by optical flow for cardiac wall motion field features. Temporal ConvNet, inspired by the Temporal Segment Network (TSN), is then applied to interpret these motion field features, independent of traditional cardiac parameter curves or specific key phase frame inputs. RESULTS: Employing five-fold cross-validation, our SVM classifier demonstrated high performance, with a sensitivity of 93.13%, specificity of 83.61%, precision of 88.52%, and an F1 score of 90.39%. When compared with other studies using the HMC-QU datasets, these Fig s stand out, underlining our method's effectiveness. The classifier also attained an overall accuracy of 89.25% and Area Under the Curve (AUC) of 95%, reinforcing its potential for reliable RWMA detection in echocardiographic analysis. CONCLUSIONS: This research not only demonstrates a novel technique but also contributes a more comprehensive and precise tool for early myocardial infarction diagnosis.