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Background: Patients with unprotected left main (UPLM) disease who underwent percutaneous coronary intervention (PCI) were found to have inconsistent results compared to those treated with coronary artery bypass grafting (CABG). Methods: We identified and enrolled randomized controlled trials (RCTs) and observational studies (OSs) comparing PCI versus CABG for UPLM disease. A meta-analysis was performed using Stata 17.0. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs). Additionally, all-cause death, cardiac death, myocardial infarction (MI), stroke, target vessel revascularization (TVR), and stent thrombosis (ST) were included as secondary endpoints. The odds ratios and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were implemented if I 2 > 50% or p < 0.01. Publication bias analysis was conducted if more than 10 studies were included. Results: A total of 5 RCTs and 18 OSs involving 35,409 patients were included. The CABG strategy had a significantly lower incidence of MACCEs, primarily due to TVR. A significantly lower stroke rate was observed with the PCI strategy, as well as a significantly lower all-cause death, cardiac death, MI, and ST rate compared with the CABG strategy. Conclusions: MACCE rates were significantly lower in patients who underwent CABG, primarily due to TVR, but stroke rates were higher. RCTs with different study types need further investigation to confirm the most effective strategy.
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Background: Side branch (SB) occlusion after main vessel stenting is the main complication in treating coronary bifurcation lesions by provisional stenting. The Jailed Wire Technique (JWT), recommended by the European Bifurcation Club, is a standard technique to deal with this issue. The Jailed Balloon Technique (JBT) has been found to be more effective than the JWT in clinical practice by some interventionists, but it has not been widely accepted. In this meta-analysis, we compared the efficacy and safety of JBT and JWT. Methods: The literature comparing JBT and JWT was systematically reviewed. Stata/MP 17.0 was used to perform a meta-analysis. The primary endpoints were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). The secondary endpoints were SB occlusion and SB dissection. Aggregated odds ratios and 95% confidence intervals were calculated. A sensitivity analysis was conducted if I 2 was > 50% or p < 0.01. Results: Thirteen studies involving 1789 patients were enrolled. JBT was found to have a significantly lower incidence of MACE, SB occlusion and dissection. The incidence of cardiac death, MI and TLR were also lower in the JBT group, though the differences were not significant. Conclusions: JBT prevents SB occlusion more effectively and does not increase immediate or long-term complications. JBT, or its modified versions, can be used to treat SBs with a high risk of occlusion.
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Despite a decade of extensive research and clinical insights, percutaneous coronary intervention strategies for coronary bifurcation lesions have remained a challenging and highly debated area. This article presents a review of the latest findings and advances in defining and classifying coronary bifurcation lesions, in vitro studies, intracoronary imaging, stenting strategies, and the deployment of drug-coated balloons. Based on current evidence, this review provides recommendations for interventional cardiologists to develop individualized interventional strategies and enhance the efficiency of stenting procedures.
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Coronary bifurcation lesions remain one of the most challenging lesions for cardiology interventionists. The provisional stenting strategy has been regarded as the first option for most of these lesions. However, the main complication of this technique is side branch (SB) occlusion, which could lead to a peri-procedural myocardial infarction or even death. Various studies have focused on addressing this issue, but there are no definitive guidelines in the literature to treat these lesions. There isn't enough clinical evidence from randomized controlled trial or two-arm cohort studies to illustrate which techniques provide the best outcomes. In this review, we summarize the mechanisms, independent predictors and predictive models of SB occlusion, and review seventeen techniques involving SB protection and occlusion rescue. Every technique was evaluated according to related bench tests, clinical studies and our own clinical experiences. The aim of this review is to provide interventionists with new insights for the treatment of coronary bifurcation lesions.
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Background: Provisional stenting is the preferred strategy for non-left main bifurcation lesions. However, its superiority over planned double stenting for unprotected left main distal bifurcation (UPLMB) lesions remains unclear. Previous studies have reported conflicting results. Methods: Randomised controlled trials (RCTs) and observational studies comparing the outcomes of provisional stenting to planned double stenting for UPLMB lesions were identified. The primary endpoint was major adverse cardiac events (MACE). The secondary endpoints were myocardial infarction (MI), target vessel revascularisation (TVR), target lesion revascularisation (TLR), all-cause death, cardiac death and stent thrombosis (ST). Aggregated odds ratios (OR) and 95% confidence intervals were calculated. A sensitivity analysis was conducted if I 2 was > 50% or p < 0.01. Publication bias analysis was considered if more than 10 studies were enrolled. Results: Two RCTs and 19 observational studies comprising 11,672 patients were enrolled. Provisional stenting had a significantly lower incidence of MACE, mainly driven by TLR and TVR. Double stenting had a significantly lower incidence of cardiac death. In addition, patients undergoing provisional stenting had a lower tendency towards the occurrence of MI, while patients undergoing double stenting had a lower tendency towards all-cause death and ST. Conclusions: A provisional stenting strategy was associated with lower MACE, TVR and TLR but higher cardiac death. Further investigation is needed through RCTs to assess which strategy performs better.
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Compromised mitophagy and mitochondrial homeostasis are major contributors for the etiology of cardiac aging, although the precise underlying mechanisms remains elusive. Shank3, a heart-enriched protein, has recently been reported to regulate aging-related neurodegenerative diseases. This study aimed to examine the role of Shank3 in the pathogenesis of cardiac senescence and the possible mechanisms involved. Cardiac-specific conditional Shank3 knockout (Shank3CKO) mice were subjected to natural aging. Mitochondrial function and mitophagy activity were determined in vivo, in mouse hearts and in vitro, in cardiomyocytes. Here, we showed that cardiac Shank3 expression exhibited a gradual increase during the natural progression of the aging, accompanied by overtly decreased mitophagy activity and a decline in cardiac function. Ablation of Shank3 promoted mitophagy, reduced mitochondria-derived superoxide (H2O2 and O2â¢-) production and apoptosis, and protected against cardiac dysfunction in the aged heart. In an in vitro study, senescent cardiomyocytes treated with D-gal exhibited reduced mitophagy and significantly elevated Shank3 expression. Shank3 knock-down restored mitophagy, leading to increased mitochondrial membrane potential, decreased mitochondrial oxidative stress, and reduced apoptosis in senescent cardiomyocytes, whereas Shank3 overexpression mimicked D-gal-induced mitophagy inhibition and mitochondrial dysfunction in normally cultured cardiomyocytes. Mechanistically, the IP assay revealed that Shank3 directly binds to CaMKII, and this interaction was further increased in the aged heart. Enhanced Shank3/CaMKII binding impedes mitochondrial translocation of CaMKII, resulting in the inhibition of parkin-mediated mitophagy, which ultimately leads to mitochondrial dysfunction and cardiac damage in the aged heart. Our study identified Shank3 as a novel contributor to aging-related cardiac damage. Manipulating Shank3/CaMKII-induced mitophagy inhibition could thus be an optional strategy for therapeutic intervention in clinical aging-related cardiac dysfunctions.
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Cardiopatías , Mitofagia , Animales , Ratones , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Cardiopatías/metabolismo , Peróxido de Hidrógeno/metabolismo , Proteínas de Microfilamentos/metabolismo , Mitofagia/fisiología , Miocitos Cardíacos/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Carotid atherosclerosis by ultrasound scanning can be considered as an ideal window to reflect systemic artery atherosclerosis, which has aroused wide concern for predicting the severity of coronary artery atherosclerosis clinically. Ultrasound radio frequency (RF) data technology has enabled us to evaluate the carotid structure and elastic function precisely, for predicting the severity of coronary artery atherosclerosis. METHODS: Patients with suspected coronary artery disease (CAD) underwent coronary angiography and were assigned to four groups according to whether atherosclerotic plaque was found or not and it caused stenosis. Carotid artery intima-media thickness (IMT) and arterial stiffness were investigated by quality intima-media thickness (QIMT) and quality arterial stiffness (QAS) techniques during ultrasound scanning. Univariable and multivariable modeling were used to investigate correlations of carotid parameters to coronary artery atherosclerosis. Receive operating characteristic (ROC) curves were used to evaluate diagnostic performance of these ultrasound variables. RESULTS: Carotid IMT and stiffness variables pulse wave velocity (PWV), α, ß and compliance coefficient (CC) were statistically different between every two-group's comparisons. IMT correlated with stiffness variables significantly with r = 0.70, 0.77, 0.63, and -0.39, respectively. All variables correlated with the severity of coronary atherosclerosis with the odd ratio (OR) of 1.73, 1.67, 1.19, 1.23, and 0.56 accordingly as IMT, PWV, α, ß and CC were concerned. The AUC of IMT, PWV, α, ß and CC were 0.9257, 0.8910, 0.8016, 0.9383, 0.8581 with correctly classified rate of 88.16%, 83.77%, 78.07%, 86.84%, and 81.58%, respectively. CONCLUSIONS: Carotid artery IMT and stiffness variable PWV, α, ß and CC presented favorable predicting and differentiating values for patients with coronary atherosclerosis of different severity.
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Aterosclerosis , Enfermedad de la Arteria Coronaria , Arterias Carótidas , Grosor Intima-Media Carotídeo , Humanos , Análisis de la Onda del PulsoAsunto(s)
Enfermedades Transmisibles , Pandemias , Brotes de Enfermedades , Humanos , Habitaciones de Pacientes , SARS-CoV-2RESUMEN
Background: Although provisional stenting strategy based on jailed balloon side branch (SB) protection could be useful for high-risk bifurcation lesion in certain clinical scenarios, its complexity still gives rise to procedure complications. We proposed a novel strategy, the jailed balloon proximal optimization technique (JB-POT), to simplify the procedures in treating complex coronary bifurcation lesions (CBLs). The present study was designed to verify the safety and efficacy of JB-POT under bench testing and clinical circumstances. Methods: After a stent was deployed in main vessel (MV) with a balloon jailed in SB, POT and post-dilation of the stent were performed without retrieving the jailed balloon. A re-POT was performed 2 mm away from SB branching point to minimize proximal stent malapposition. The JB-POT procedure was performed on 10 samples of a silicone bifurcation bench model, and optical coherence tomography (OCT) was utilized to evaluate stent deployment. From December 2018 to July 2021, a total of 28 consecutive patients with true CBLs treated with JB-POT were enrolled. Immediate procedure results were observed, and clinical follow-ups were performed. Results: The bench test showed that JB-POT did not induce significant stent malapposition, underexpansion or distortion, as indexed by the malapposition rate, minimum stent area (MSA), eccentricity index and symmetry index determined through OCT. Under clinical circumstances, JB-POT did not induce significant malapposition, underexpansion or distortion. Among the 30 lesions, there was no primary endpoint event defined as SB occlusion, need to rewire the SB with a polymer-covered guide wire, or failure to retrieve a jailed wire or balloon. One rewiring event and 0 double stenting events occurred as secondary endpoint events. One patient died of heart failure in the 8th month after discharge. Conclusions: The JB-POT protocol, which tremendously simplifies the current standard provisional stenting procedure in complicated bifurcation lesions, shows acceptability in safety and efficacy. Hence, it might become an applicable strategy for treating high-risk bifurcation lesions, especially those with multiple risked SBs.
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A previous calcium scoring system using circumferential angle, thickness, and length of coronary calcium by OCT could assist in predicting stent under-expansion. However, this scoring system only reflects the calcification distribution within a single cross-section and fails to consider the lumen's original size. The current study aims to investigate whether novel parameters to quantify calcium lesions, including calcium burden, area, and volume assessed by optical coherence tomography (OCT), could predict stent under-expansion related to calcium lesions. Consecutive patients admitted between March 10th to October 19th 2021 with calcified coronary lesions undergoing percutaneous coronary intervention (PCI) with OCT guidance were screened for inclusion. The calcium burden, area, and volume of the target lesions were measured using OCT at pre-PCI. After successful stent implantation, stent expansion at the corresponding lesions was also measured by OCT. A total of 125 patients who underwent OCT-guided PCI were included in this study. While the calcium grades by angiography failed to show a significant correlation with stent expansion, maximum and average calcium burden, maximum calcium area, and calcium volume exhibited a moderate correlation with stent expansion. According to the receiver operating characteristic curves, the optimal cutoffs of calcium volume and area for predicting stent under-expansion were 4.37 mm3 and 2.48 mm2 , respectively. Calcium burden, area, and volume by OCT are more favorable predictors of stent under-expansion given its better performance than calcium grades by angiography. Using cutoffs of calcium area and volume could identify high-risk patients of under-expansion and might guide future clinical practice.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Calcio , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/terapia , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Humanos , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Stents , Tomografía de Coherencia Óptica , Resultado del TratamientoRESUMEN
Sepsis is a serious complication after infection, whose further development may lead to multiple organ dysfunction syndrome and so on. It is an important cause of death in critically ill patients who suffered an infection. Sepsis cardiomyopathy is a common complication that exacerbates the prognosis of patients. At present, though the pathogenesis of sepsis cardiomyopathy is not completely clear, in-depth study of the pathogenesis of sepsis cardiomyopathy and the discovery of its potential therapeutic targets may decrease the mortality of sepsis patients and bring clinical benefits. This article reviews mitochondrial dysfunction, mitophagy, oxidation stress, and other mechanisms in sepsis cardiomyopathy.
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Cardiomiopatías , Sepsis , Cardiomiopatías/patología , Humanos , Mitocondrias/patología , Mitofagia , Insuficiencia Multiorgánica , Sepsis/complicacionesRESUMEN
BACKGROUND: miR-205 is important for oxidative stress, mitochondrial dysfunction, and apoptosis. The roles of miR-205 in cardiac ischemia/reperfusion (I/R) injury remain unknown. The aim of this research is to reveal whether miR-205 could regulate cardiac I/R injury by focusing upon the oxidative stress, mitochondrial function, and apoptosis. METHODS: Levels of miR-205 and Rnd3 were examined in the hearts with I/R injury. Myocardial infarct size, cardiac function, oxidative stress, mitochondria function, and cardiomyocyte apoptosis were detected in mice with myocardial ischemia/reperfusion (MI/R) injury. The primary neonatal cardiomyocytes underwent hypoxia/reoxygenation (H/R) to simulate MI/R injury. RESULTS: miR-205 levels were significantly elevated in cardiac tissues from I/R in comparison with those from Sham. In comparison with controls, levels of Rnd3 were significantly decreased in the hearts from mice with MI/R injury. Furthermore, inhibiting miR-205 alleviated MI/R-induced apoptosis, reduced infarct size, prevented oxidative stress increase and mitochondrial fragmentation, and improved mitochondrial functional capacity and cardiac function. Consistently, overexpression of miR-205 increased infarct size and promoted apoptosis, oxidative stress, and mitochondrial dysfunction in mice with MI/R injury. In cultured mouse neonatal cardiomyocytes, downregulation of miR-205 reduced oxidative stress in H/R-treated cardiomyocytes. Finally, inhibiting Rnd3 ablated the cardioprotective effects of miR-205 inhibitor in MI/R injury. CONCLUSIONS: We conclude that inhibiting miR-205 reduces infarct size, improves cardiac function, and suppresses oxidative stress, mitochondrial dysfunction, and apoptosis by promoting Rnd3 in MI/R injury. miR-205 inhibitor-induced Rnd3 activation is a valid target to treat MI/R injury.
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Apoptosis/genética , MicroARNs/genética , Mitocondrias/genética , Isquemia Miocárdica/genética , Estrés Oxidativo/genética , Animales , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Infarto del Miocardio/metabolismo , Isquemia Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
BACKGROUND: Malignant obstructive jaundice (MOJ) has a low immediate surgery rate (10-20%) and a poor post-resection survival rate. Although several clinical results have demonstrated the safety and efficacy of stent placement combined with radioactive seeds, the existing implantation methods are time consuming and prone to error. In this study, we introduced a self-made delivery system and novel implantation method for a self-expandable metallic stent (SEMS) with 125I seed strand and evaluated its feasibility and efficacy in MOJ patients. METHODS: Our self-made delivery system was applied to 61 patients (39 males and 22 females, mean age 66.36±10.73 years) from October 2018 to June 2020 in our center with a novel implantation method. The preparation and manipulation processes were described in detail. Technical and clinical successes were recorded, and stent patency and overall survival (OS) were assessed. A P value of less than 0.05 indicated a significant difference. RESULTS: Stents with 125I seed strands were successfully placed in all 61 participants with our novel implantation method. The clinical success rate was 96.7%, and no severe procedure-related complications were found except bile leakage through puncture in 1 participant. The median duration of primary stent patency was 120 (37, 233.5) days, and the median OS was 169 (41, 270) days. CONCLUSIONS: Our self-made delivery system with a novel SEMS implantation method with 125I seed strand was feasible and effective for MOJ patients and significantly simplified the current implantation approach.
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Bakuchiol (BAK), a monoterpene phenol reported to have exerted a variety of pharmacological effects, has been related to multiple diseases, including myocardial ischemia reperfusion injury, pressure overload-induced cardiac hypertrophy, diabetes, liver fibrosis, and cancer. However, the effects of BAK on hyperglycemia-caused diabetic cardiomyopathy and its underlying mechanisms remain unclear. In this study, streptozotocin-induced mouse model and high-glucose-treated cell model were conducted to investigate the protective roles of BAK on diabetic cardiomyopathy, in either the presence or absence of SIRT1-specific inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA. Our data demonstrated for the first time that BAK could significantly abate diabetic cardiomyopathy by alleviating the cardiac dysfunction, ameliorating the myocardial fibrosis, mitigating the cardiac hypertrophy, and reducing the cardiomyocyte apoptosis. Furthermore, BAK achieved its antifibrotic and antihypertrophic actions by inhibiting the TGF-ß1/Smad3 pathway, as well as decreasing the expressions of fibrosis- and hypertrophy-related markers. Intriguingly, these above effects of BAK were largely attributed to the remarkable activation of SIRT1/Nrf2 signaling, which eventually strengthened cardiac antioxidative capacity by elevating the antioxidant production and reducing the reactive oxygen species generation. However, all the beneficial results were markedly abolished with the administration of EX527, SIRT1 siRNA, or Nrf2 siRNA. In summary, these novel findings indicate that BAK exhibits its therapeutic properties against hyperglycemia-caused diabetic cardiomyopathy by attenuating myocardial oxidative damage via activating the SIRT1/Nrf2 signaling.
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Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fenoles/farmacología , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Animales , Antioxidantes/metabolismo , Carbazoles/farmacología , Supervivencia Celular/efectos de los fármacos , Colágeno/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/etiología , Glucosa/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Miocardio/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Factor 2 Relacionado con NF-E2/antagonistas & inhibidores , Factor 2 Relacionado con NF-E2/genética , Fenoles/uso terapéutico , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/genéticaRESUMEN
Cardiovascular diseases are a main cause of mortality whose prevalence continues to increase worldwide. Long non-coding RNAs (lncRNAs) regulate a variety of biological processes by modifying and regulating transcription of coding genes, directly binding to proteins and even coding proteins themselves. LncRNAs play key roles in the occurrence and development of myocardial infarction, heart failure, myocardial hypertrophy, arrhythmias and other pathological processes that significantly affect the prognosis and survival of patients with cardiovascular diseases. We here review the latest research on lncRNAs in cardiovascular diseases as a basis to formulate future research on prevention and treatment of cardiovascular diseases.
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Enfermedades Cardiovasculares/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/fisiología , Animales , Apoptosis , Arritmias Cardíacas/metabolismo , Aterosclerosis/metabolismo , Autofagia , Biomarcadores/metabolismo , Cardiología/tendencias , Cardiomiopatía Dilatada/metabolismo , Enfermedades Cardiovasculares/patología , Proliferación Celular , Insuficiencia Cardíaca , Histonas/metabolismo , Humanos , Inflamación , Metabolismo de los Lípidos , Metilación , Infarto del Miocardio/metabolismo , Pronóstico , Unión Proteica , Transducción de Señal , Resultado del TratamientoRESUMEN
INTRODUCTION: The anthracycline doxorubicin (DOX) has proved to be one of the most widely used and most effective antitumor drugs since its emergence in the 1960s. However, the utility of DOX is compromised by its potential lethal cardiotoxicity. In this review we summarize development in prevention and management of DOX-induced cardiotoxicity comprehensively. BACKGROUND: Strategies to enhance DOX efficacy in cancer cells while minimizing associated cardiotoxicity may prove clinically valuable. Employment of DOX derivatives, including currently available mitoxantrone and epirubicin, has been testified in several clinical trials. Several cardioprotective agents, including dexrazoxane, statins, angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, and etc., have been developed and tested in animal and clinical trials. CONCLUSION: Several strategies have been reported on the prevention and management of DOX-elicited cardiotoxicity, and many of them await verification from large scale clinical trials. Dexrazoxane has been approved to prevent and treat side effects of DOX, although concerns still exist that it might increase incidence of some kind of malignant tumors. Promising findings in autophagy, RNA binding protein quaking and statins encourage further research developing strategies by which heart protection and cancer cell killing are achieved simutaneously.
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Antibióticos Antineoplásicos/efectos adversos , Cardiotónicos/farmacología , Cardiotoxicidad/prevención & control , Doxorrubicina/efectos adversos , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
BACKGROUND: Inferior vena cava filters (IVCF) are frequently used for preventing pulmonary embolism (PE) following deep venous thromboembolism. OBJECTIVES: The present study was designed to investigate whether IVCF could prevent or impede the occurrence of bone cement implantation syndrome (BCIS), since PE is considered as the central mechanism of BCIS. MATERIALS AND METHODS: Fifteen sheep were divided into three groups: bone cement free (BCF) group, cement implantation (CI) group and IVCF group. In all the groups, an osteotomy proximal to the greater trochanter of left femur was carried out. In BCF group, the femoral canal was not reamed out or packed with any bone cement. In CI and IVCF groups, the left femoral canals were packed with bone cement, to simulate the cementing procedures carried out in hip replacement. An OptEase(®) filter was placed and released in inferior vena cava, prior to packing cement in the femoral canal in IVCF group, while the IVCF was not released in the CI group. The BCF group was considered as control. RESULTS: Systolic blood pressure (SBP), saturation of oxygen (SaO2) and partial pressure of carbon dioxide (PaCO2) declined significantly 10 min after the bone cement packing, in CI group, compared to those in BCF group. This was accompanied by a rise in the arterial pH. However, IVCF prevented those changes in the CI group. On ultrasonography, there were dotted echoes in right atrium in the CI group, after bone cement packing, while such echoes were hardly seen in the IVCF group. CONCLUSION: This study demonstrates that IVCF could prevent BCIS effectively, and, as a corollary, suggests that PE represents the leading cause of the constellation of BCIS symptoms.
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Hearts of diabetic individuals are susceptible to ischemia/reperfusion (I/R) injury. The RNA-binding protein Quaking (QKI) is known to link intracellular signaling to cellular survival and QKI dysregulation may contribute to human diseases. However, the function of QKI in diabetic hearts remains unknown. The current study attempted to identify new molecular mechanisms that potentially contribute to the susceptibility to ischemic injury in diabetic myocardium. Diabetic ob/ob mice or wild-type C57BL/6J mice were subjected to in vivo myocardial I/R. Myocardial infarct size and apoptosis, QKI5 and FoxO1 expression, nitrosative stress (NS) and ER stress were compared. Knockdown of FoxO1 was obtained by intramyocardial injection of FoxO1 specific small interfering RNA (siRNA, 20µg), and upregulation of QKI5 was acquired by injecting adenovirus encoding-QKI5. Obvious NS stress was observed in the myocardium of ob/ob mice represented by elevated iNOS expression, total NO content and nitrotyrosine content. Administration of 1400W or M40401 partly reduced the caspase-3 activity in ob/ob myocardium encountering I/R (P<0.05). Higher ER stress was also observed represented by increased p-PERK, p-eIF2α and expression of CHOP in ob/ob myocardium. ER stress inhibitor did not affect the excessive NS stress, but partially reduced I/R-induced caspase-3 activity in ob/ob hearts (P<0.05). FoxO1 was overactivated in ob/ob myocardium, and knockdown of FoxO1 attenuated both levels of NS stress and ER stress (P<0.05). Furthermore, QKI5 expression was deficient in ob/ob myocardium. Upregulation of QKI5 diminished FoxO1 expression together with NS and ER stress in ob/ob myocardium, further reducing MI/R injury. Finally, QKI5 overexpression destabilized FoxO1 mRNA in cardiomyocytes. These results suggested that QKI5 deficiency contributed to the overactivation of FoxO1 in ob/ob animals and subsequently magnified nitrosative stress and ER stress, which enhances the ischemic intolerance of diabetic hearts.
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Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Estrés del Retículo Endoplásmico , Factores de Transcripción Forkhead/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Proteínas de Unión al ARN/metabolismo , Animales , Apoptosis , Diabetes Mellitus Experimental/metabolismo , Regulación hacia Abajo , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/genética , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Isquemia Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/patología , Nitrosación , Estabilidad Proteica , ARN Mensajero/genética , ARN Mensajero/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: To validate the Andon KD-5917 automatic upper arm blood pressure monitor according to the European Society of Hypertension International Protocol revision 2010. MATERIALS AND METHODS: Sequential same-left-arm measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained in 33 participants using the mercury sphygmomanometer and the test device. According to the validation protocol, 99 pairs of test device and reference blood pressure measurements (three pairs for each of the 33 participants) were obtained in the study. RESULTS: The device produced 73, 98, and 99 measurements within 5, 10, and 15 mmHg for SBP and 86, 98, and 99 for DBP, respectively. The mean ± SD device-observer difference was 3.07 ± 3.68 mmHg for SBP and -0.89 ± 3.72 mmHg for DBP. The number of patients with two or three of the device-observer difference within 5 mmHg was 26 for SBP and 29 for DBP, and no patient had a device-observer difference within 5 mmHg. CONCLUSION: The Andon KD-5917 automatic upper arm blood pressure monitor can be recommended for clinical use and self-measurement in an adult population on the basis of the European Society of Hypertension International Protocol revision 2010.