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1.
Front Cardiovasc Med ; 10: 1132626, 2023.
Article in English | MEDLINE | ID: mdl-37424915

ABSTRACT

Introduction: Percutaneous closure of the left atrial appendage (LAA) facilitates stroke prevention in patients with atrial fibrillation. Optimal device selection and positioning are often challenging due to highly variable LAA shape and dimension and thus require accurate assessment of the respective anatomy. Transesophageal echocardiography (TEE) and x-ray fluoroscopy (XR) represent the gold standard imaging techniques. However, device underestimation has frequently been observed. Assessment based on 3-dimensional computer tomography (CTA) has been reported as more accurate but increases radiation and contrast agent burden. In this study, the use of non-contrast-enhanced cardiac magnetic resonance imaging (CMR) to support preprocedural planning for LAA closure (LAAc) was investigated. Methods: CMR was performed in thirteen patients prior to LAAc. Based on the 3-dimensional CMR image data, the dimensions of the LAA were quantified and optimal C-arm angulations were determined and compared to periprocedural data. Quantitative figures used for evaluation of the technique comprised the maximum diameter, the diameter derived from perimeter and the area of the landing zone of the LAA. Results: Perimeter- and area-based diameters derived from preprocedural CMR showed excellent congruency compared to those measured periprocedurally by XR, whereas the respective maximum diameter resulted in significant overestimation (p < 0.05). Compared to TEE assessment, CMR-derived diameters resulted in significantly larger dimensions (p < 0.05). The deviation of the maximum diameter to the diameters measured by XR and TEE correlated well with the ovality of the LAA. C-arm angulations used during the procedures were in agreement with those determined by CMR in case of circular LAA. Discussion: This small pilot study demonstrates the potential of non-contrast-enhanced CMR to support preprocedural planning of LAAc. Diameter measurements based on LAA area and perimeter correlated well with the actual device selection parameters. CMR-derived determination of landing zones facilitated accurate C-arm angulation for optimal device positioning.

3.
Front Cardiovasc Med ; 9: 931959, 2022.
Article in English | MEDLINE | ID: mdl-36324746

ABSTRACT

Preprocedural planning and periprocedural guidance based on image fusion are widely established techniques supporting the interventional treatment of structural heart disease. However, these two techniques are typically used independently. Previous works have already demonstrated the benefits of integrating planning details into image fusion but are limited to a few applications and the availability of the proprietary tools used. We propose a vendor-independent approach to integrate planning details into periprocedural image fusion facilitating guidance during interventional treatment. In this work, we demonstrate the feasibility of integrating planning details derived from computer tomography and magnetic resonance imaging into periprocedural image fusion with open-source and commercially established tools. The integration of preprocedural planning details into periprocedural image fusion has the potential to support safe and efficient interventional treatment of structural heart disease.

4.
Med Sci Monit ; 28: e935455, 2022 May 23.
Article in English | MEDLINE | ID: mdl-35673773

ABSTRACT

BACKGROUND We aimed to investigate the impact of microalbuminuria complicated with low estimate glomerular filtration rate (eGFR) on the incidence and prognosis of contrast-induced acute kidney injury (CI-AKI) in patients with coronary artery disease after coronary intervention. MATERIAL AND METHODS A total of 943 patients were enrolled in the study. Based on microalbumin/creatinine (ACR) measurements, the patients were divided into a microalbuminuria cohort (MA; 222 patients) and a normal albuminuria cohort (NA; 721 patients). According to eGFR levels, the cohorts were further subdivided into normal, mild, moderate, and severe renal dysfunction groups. The basic data and indicators of all enrolled patients were collected. The patients were followed up at 30 days, 6 months, 1 year, and 3 years after surgery. RESULTS The overall incidence of CI-AKI in the MA cohort was higher than that in the NA cohort (17.6% vs 8.2%, P.


Subject(s)
Acute Kidney Injury , Albuminuria , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Albuminuria/complications , Contrast Media/adverse effects , Creatinine , Glomerular Filtration Rate , Humans , Risk Factors
5.
Front Endocrinol (Lausanne) ; 13: 817176, 2022.
Article in English | MEDLINE | ID: mdl-35273567

ABSTRACT

Background: Triglyceride-glucose (TyG) index is a reliable and specific biomarker for insulin resistance and is associated with renal dysfunction. The present study sought to explore the relationship between TyG index and the incidence of contrast-induced nephropathy (CIN) in non-ST elevation acute coronary syndrome (NSTE-ACS) patients implanted with drug-eluting stents (DESs). Methods: A total of 1108 participants were recruited to the study and assigned to two groups based on occurrence of CIN. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Baseline characteristics and incidence of CIN were compared between the two groups. Logistic regression analysis was performed to evaluate the relationship between TyG index and CIN. Results: The results showed that 167 participants (15.1%) developed CIN. Subjects in the CIN group had a significantly higher TyG index compared with subjects in the non-CIN group (8.9 ± 0.7 vs. 9.3 ± 0.7, P<0.001). TyG index was significantly correlated with increased risk of CIN after adjusting for confounding factors irrespective of diabetes mellitus status and exhibited a J-shaped non-linear association. Subgroup analysis showed a significant gender difference in the relationship between TyG index and CIN. Receiver operating characteristic (ROC) curve analysis indicated that the risk assessment performance of TyG index was superior compared with other single metabolic indexes. Addition of TyG index to the baseline model increased the area under the curve from 0.713 (0.672-0.754) to 0.742 (0.702-0.782) and caused a reclassification improvement of 0.120 (0.092-0.149). Conclusion: The findings from the present study show that a high TyG index is significantly and independently associated with incidence of CIN in NSTE-ACS patients firstly implanted with DESs. Routine preoperative assessment of TyG index can alleviate CIN and TyG index provides a potential target for intervention in prevention of CIN.


Subject(s)
Acute Coronary Syndrome , Kidney Diseases , Acute Coronary Syndrome/epidemiology , Blood Glucose/metabolism , Female , Glucose , Humans , Incidence , Male , Retrospective Studies , Risk Factors , Triglycerides
6.
Life Sci ; 274: 119366, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33741419

ABSTRACT

AIMS: N6-methyladenosine (m6A) is the most prevalent internal chemical RNA modification in mammal mRNAs. Accumulating evidence has shown the critical role of m6A in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, whether m6A participates in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. The present study aims to explore the role of key transferase METTL3, in the development of HPH. MATERIALS AND METHODS: Pulmonary artery smooth muscle cells (PASMCs) and hypoxic rat models were used to research the METTL3-mediated m6A in HPH. EdU, transwell and TUNEL were performed to evaluate the proliferation, migration and apoptosis rates. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A level of PTEN mRNA. RNA immunoprecipitation was used to detect the interaction between METTL3 and PTEN mRNA. KEY FINDINGS: Both METTL3 mRNA and protein were found abnormally upregulated in vivo and in vitro. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration. In addition, m6A binding protein YTHDF2 was found significantly increased in PASMCs under hypoxia. YTHDF2 recognized METTL3 mediated m6A modified PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. SIGNIFICANCE: METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH.


Subject(s)
Adenosine/analogs & derivatives , Hypoxia/physiopathology , Methyltransferases/metabolism , Myocytes, Smooth Muscle/pathology , Pulmonary Arterial Hypertension/pathology , Pulmonary Artery/pathology , RNA, Messenger/metabolism , Adenosine/chemistry , Animals , Apoptosis , Cell Proliferation , Male , Methylation , Methyltransferases/genetics , Myocytes, Smooth Muscle/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Pulmonary Arterial Hypertension/metabolism , Pulmonary Artery/metabolism , RNA, Messenger/chemistry , RNA, Messenger/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction
7.
World J Diabetes ; 12(2): 124-137, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33594332

ABSTRACT

BACKGROUND: Endothelial dysfunction, a hallmark of diabetes, is a critical and initiating contributor to the pathogenesis of diabetic cardiovascular complications. However, the underlying mechanisms are still not fully understood. Ferroptosis is a newly defined regulated cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Although the involvement of ferroptosis in disease pathogenesis has been shown in cancers and degenerative diseases, the participation of ferroptosis in the pathogenesis of diabetic endothelial dysfunction remains unclear. AIM: To examine the role of ferroptosis in diabetes-induced endothelial dysfunction and the underlying mechanisms. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG), interleukin-1ß (IL-1ß), and ferroptosis inhibitor, and then the cell viability, reactive oxygen species (ROS), and ferroptosis-related marker protein were tested. To further determine whether the p53-xCT (the substrate-specific subunit of system Xc-)-glutathione (GSH) axis is involved in HG and IL-1ß induced ferroptosis, HUVECs were transiently transfected with p53 small interfering ribonucleic acid or NC small interfering ribonucleic acid and then treated with HG and IL-1ß. Cell viability, ROS, and ferroptosis-related marker protein were then assessed. In addition, we detected the xCT and p53 expression in the aorta of db/db mice. RESULTS: It was found that HG and IL-1ß induced ferroptosis in HUVECs, as evidenced by the protective effect of the ferroptosis inhibitors, Deferoxamine and ferrostatin-1, resulting in increased lipid ROS and decreased cell viability. Mechanistically, activation of the p53-xCT-GSH axis induced by HG and IL-1ß enhanced ferroptosis in HUVECs. In addition, a decrease in xCT and the presence of de-endothelialized areas were observed in the aortic endothelium of db/db mice. CONCLUSION: Ferroptosis is involved in endothelial dysfunction and p53-xCT-GSH axis activation plays a crucial role in endothelial cell ferroptosis and endothelial dysfunction.

8.
Cell Signal ; 78: 109843, 2021 02.
Article in English | MEDLINE | ID: mdl-33253911

ABSTRACT

NLRP3 inflammasome-mediated vascular EC pyroptosis is a key event in the pathogenesis of atherosclerosis. Dysregulation of glucose metabolism is involved in EC dysfunction. Although BDNF plays a protective role in vascular endothelium physiological activity, the mechanisms underlying this activity are not yet clear. In this study, we investigated the role of BDNF in NLRP3 inflammasome-mediated EC pyroptosis and its associated reprogramming of glucose metabolism. HUVECs were treated with human rBDNF under ox-LDL stimulation. rBDNF alleviated ox-LDL-induced NLRP3 inflammasome formation and HUVEC pyroptosis, as evaluated by NLRP3, caspase1-p10, interleukin-18, and interleukin-1ß protein levels, co-localization of NLRP3 and apoptosis-associated speck-like protein, and lactate dehydrogenase release. These effects were prevented by tropomyosin receptor kinase B inhibition and KLF2 silencing. The hyper-activation of glycolysis induced by ox-LDL-induced was mitigated by rBDNF via KLF2 as assessed by glucose uptake, lactate production, and extracellular acidification rate. In addition, the BDNF/KLF2 pathway preserved the mitochondrial membrane potential, intracellular reactive oxygen species generation, electron transport chain processing, oxygen consumption rate, and adenosine triphosphate production. Furthermore, KLF2 interacted with HK1 and HK1 overexpression evoked NLRP3 inflammasome formation. At the clinical level, plasma BDNF and lactate levels were measured in 274 patients who underwent computed tomography and coronary angiography for CAD diagnosis. Patients with CAD had lower BDNF and increased lactate levels than those without CAD. In 94 patients with CAD, circulating BDNF levels were inversely associated with lactate levels. In the receiver operating characteristic analysis of CAD, the areas under the curves for 1/BDNF, lactate, and 1/BDNF+lactate were 0.707, 0.702, and 0.753 respectively. These results indicate that BDNF and lactate are linked in atherosclerotic patients, and BDNF inhibits ox-LDL induced NLRP3 inflammasome formation and pyroptosis in HUVECs via KLF2/HK1-mediated glucose metabolism modulation and mitochondrial homeostasis preservation.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Cellular Reprogramming , Glucose/metabolism , Hexokinase/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Inflammasomes/metabolism , Kruppel-Like Transcription Factors/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis , Signal Transduction , Brain-Derived Neurotrophic Factor/genetics , Glucose/genetics , Hexokinase/genetics , Humans , Inflammasomes/genetics , Kruppel-Like Transcription Factors/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/genetics
9.
Shock ; 55(2): 244-255, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33026218

ABSTRACT

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a devastating and incurable disease characterized by pulmonary vascular remodeling, resulting in right heart failure and even death. Accumulated evidence has confirmed long coding RNAs (lncRNAs) are involved in hypoxia-induced pulmonary vascular remodeling in HPH. The exact mechanism of lncRNA in hypoxic pulmonary hypertension remains unclear. METHODS: Microarray analysis was applied to investigate the profiles of lncRNA expression in pulmonary artery smooth muscle cells (PASMCs) cultured under hypoxia and normoxia condition. qRT-PCR was performed for the expression of lncRNAs, miRNA, and mRNAs, western blot analysis was employed for the detection of the expression of proteins. CCK-8 and transwell chamber assay were applied for the assessment of PASMC proliferation and migration, respectively. Besides, flow cytometry was performed for assessments of cell cycle progression. The binding between AC068039.4 and miR-26a-5p, miR-26a-5p, and TRPC6 3'UTR was detected by dual luciferase reporter assay. RESULTS: A total of 1,211 lncRNAs (698 up-regulated and 513 down-regulated) were differently expressed in hypoxia-induced PASMCs. Consistent with microarray analysis, quantitative PCR verified that AC068039.4 was obviously up-regulated in hypoxia-induced PASMCs. Knocking down AC068039.4 alleviated proliferation and migration of PASMCs and regulated cell cycle progression through inhibiting cells entering the G0/G1 cell cycle phase. Further experiment indicated AC068039.4 promoted hypoxic PASMCs proliferation via sponging miR-26-5p. In addition, transient receptor potential canonical 6 (TRPC6) was confirmed to be a target gene of miR-26a-5p. CONCLUSION: In conclusion, downregulation of lncRNA AC068039.4 inhibited pulmonary vascular remodeling through AC068039.4/miR-26a-5p/TRPC6 axis, providing new therapeutic insights for the treatment of HPH.


Subject(s)
Cell Cycle/physiology , Cell Proliferation/physiology , MicroRNAs/physiology , Myocytes, Smooth Muscle/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Artery/cytology , RNA, Long Noncoding/physiology , TRPC6 Cation Channel/physiology , Cell Hypoxia , Cells, Cultured , Gene Expression , Humans , RNA, Long Noncoding/biosynthesis , RNA, Long Noncoding/genetics
10.
Clin Appl Thromb Hemost ; 26: 1076029620944492, 2020.
Article in English | MEDLINE | ID: mdl-33032448

ABSTRACT

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Early identification of high-risk patients has an essential role in preventing CI-AKI. This study was designed to evaluate the predictive value of d-dimer, a marker of thrombosis and hypercoagulable state, for CI-AKI and prognosis in patients with STEMI. We included 400 patients with STEMI who underwent PCI. The patients were subdivided into 4 groups according to d-dimer level using the 4-quantile method. Contrast-induced acute kidney injury occurred in 66 (16.5%) patients. The incidence of CI-AKI in the highest quartile of the d-dimer groups (29.0%) was higher than that in the other 3 groups. Multivariable logistic regression showed that a low d-dimer level was significantly associated with a decreased risk of CI-AKI independent of confounding factors, with an odds ratio (OR) of 0.487 (95% CI: 0.178-0.931, P = 0.041) for those in the first quartile compared with those in the highest quartile. Age (OR: 1.047, 95% CI: 1.003-1.092), diabetes mellitus (OR: 5.896, 95% CI: 2.496-13.927), anemia (OR: 3.488, 95% CI: 1.308-9.306), and total bilirubin (OR: 0.946, 95% CI: 0.904-0.992) were independent predictors of CI-AKI. The incidence of major adverse cardiovascular and cerebral events and all-cause mortality within 30 days, 6 months, and 1 year after PCI in the highest quartile of the d-dimer groups were higher than those in the other 3 groups. In conclusion, increasing d-dimer levels were independently associated with the incidence of CI-AKI and adverse outcomes in patients with STEMI after PCI.


Subject(s)
Acute Kidney Injury/chemically induced , Contrast Media/adverse effects , Fibrin Fibrinogen Degradation Products/metabolism , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/complications , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
11.
Int J Mol Med ; 46(6): 1958-1972, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33125109

ABSTRACT

N6­methyladenosine (m6A) is the most prevalent and abundant type of internal post­transcriptional RNA modification in eukaryotic cells. Multiple types of RNA, including mRNAs, rRNAs, tRNAs, long non­coding RNAs and microRNAs, are involved in m6A methylation. The biological function of m6A modification is dynamically and reversibly mediated by methyltransferases (writers), demethylases (erasers) and m6A binding proteins (readers). The methyltransferase complex is responsible for the catalyzation of m6A modification and is typically made up of methyltransferase­like (METTL)3, METTL14 and Wilms tumor 1­associated protein. Erasers remove methylation by fat mass and obesity­associated protein and ALKB homolog 5. Readers play a role through the recognition of m6A­modified targeted RNA. The YT521­B homology domain family, heterogeneous nuclear ribonucleoprotein and insulin­like growth factor 2 mRNA­binding protein serve as m6A readers. The m6A methylation on transcripts plays a pivotal role in the regulation of downstream molecular events and biological functions, such as RNA splicing, transport, stability and translatability at the post­transcriptional level. The dysregulation of m6A modification is associated with cancer, drug resistance, virus replication and the pluripotency of embryonic stem cells. Recently, a number of studies have identified aberrant m6A methylation in cardiovascular diseases (CVDs), including cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification and pulmonary hypertension. The aim of the present review article was to summarize the recent research progress on the role of m6A modification in CVD and give a brief perspective on its prospective applications in CVD.


Subject(s)
Adenosine/analogs & derivatives , Cardiovascular Diseases/genetics , RNA/metabolism , Adenosine/metabolism , Animals , Humans , Methylation , Polymorphism, Single Nucleotide/genetics , RNA-Binding Proteins/metabolism
12.
Exp Ther Med ; 20(6): 164, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33093902

ABSTRACT

Pulmonary hypertension (PH) is a life-threatening cardiopulmonary condition caused by several pathogenic factors. All types of PH are characterized by the excessive proliferation of pulmonary artery endothelial cells and pulmonary artery smooth muscle cells, apoptosis resistance, pulmonary vascular remodeling, sustained elevated pulmonary arterial pressure, right heart failure and even death. Over the past decade, next generation sequencing, particularly RNA-sequencing, has identified some long non-coding RNAs (lncRNAs) that may act as regulators of cell differentiation, proliferation and apoptosis. Studies have shown that lncRNAs are closely associated with the development of several diseases, including cardiovascular diseases. In addition, a number of studies have reported that lncRNAs, including maternally expressed gene 3, metastasis-associated lung adenocarcinoma transcript 1, taurine upregulated 1 and cancer susceptibility candidate 2, serve important roles in the pathogenesis of PH. Despite the development of novel drug treatments, the mortality rate of PH remains high with no evident downward trend. Therefore, certain lncRNAs may be considered as therapeutic targets for the treatment of incurable PH. The present review summarizes the latest research on lncRNAs and PH, aiming to briefly describe PH-associated lncRNAs and their mechanisms of action.

13.
Biomed Res Int ; 2020: 1860268, 2020.
Article in English | MEDLINE | ID: mdl-32879878

ABSTRACT

Previous studies showed that fibrinogen-to-albumin ratio (FAR) regarded as a novel inflammatory and thrombotic biomarker was the risk factor for coronary artery disease (CAD). In this study, we sought to evaluate the relationship between FAR and severity of CAD, long-term prognosis in non-ST elevation acute coronary syndrome (NSTE-ACS) patients firstly implanted with drug-eluting stent (DES). A total of 1138 consecutive NSTE-ACS patients firstly implanted with DES from January 2017 to December 2018 were recruited in this study. Patients were divided into tertiles according to FAR levels (Group 1: ≤8.715%; Group 2: 8.715%~10.481%; and Group 3: >10.481%). The severity of CAD was evaluated using the Gensini Score (GS). The endpoints were major adverse cardiovascular events (MACE), including all-cause mortality, myocardial reinfarction, and target vessel revascularization (TVR). Positive correlation was detected by Spearman's rank correlation coefficient analysis between FAR and GS (r = 0.170, P < 0.001). On multivariate logistic analysis, FAR was an independent predictor of severe CAD (OR: 1.060; 95% CI: 1.005~1.118; P < 0.05). Multivariate Cox regression analysis indicated that FAR was an independent prognostic factor for MACE at 30 days, 6 months, and 1 year after DES implantation (HR: 1.095; 95% CI: 1.011~1.186; P = 0.025. HR: 1.076; 95% CI: 1.009~1.147; P = 0.026. HR: 1.080; 95% CI: 1.022~1.141; P = 0.006). Furthermore, adding FAR to the model of established risk factors, the C-statistic increased from 0.706 to 0.720, 0.650 to 0.668, and 0.611 to 0.632, respectively. And the models had incremental prognostic value for MACE, especially for 1-year MACE (NRI: 13.6% improvement, P = 0.044; IDI: 0.6% improvement, P = 0.042). In conclusion, FAR was associated independently with the severity of CAD and prognosis, helping to improve risk stratification in NSTE-ACS patients firstly implanted with DES.


Subject(s)
Acute Coronary Syndrome/etiology , Coronary Artery Disease/etiology , Fibrinogen/analysis , Serum Albumin/analysis , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/therapy , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Coronary Artery Disease/blood , Coronary Artery Disease/therapy , Creatine Kinase, MB Form/blood , Drug-Eluting Stents , Electrocardiography , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Troponin I/blood
14.
Biomed Res Int ; 2020: 4370832, 2020.
Article in English | MEDLINE | ID: mdl-32461988

ABSTRACT

Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (-11.81 ± 2.47 pA/pF, P < 0.05 vs. CON, n = 10). Ba2+(50 µM) decreased Kir2.x currents (-2.13 ± 0.23 pA/pF, P < 0.05 vs. CON, n = 10), which were promoted by PDGF-BB (-6.98 ± 1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor ß (PDGF-BBRß) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRß through activation of cAMP-PKA signaling in RASMCs.


Subject(s)
Becaplermin/pharmacology , Cyclic AMP-Dependent Protein Kinases/metabolism , Muscle, Smooth, Vascular/cytology , Potassium Channels, Inwardly Rectifying , Animals , Aorta, Thoracic/cytology , Cells, Cultured , Colforsin/pharmacology , HEK293 Cells , Humans , Male , Potassium Channels, Inwardly Rectifying/drug effects , Potassium Channels, Inwardly Rectifying/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
15.
BMC Cardiovasc Disord ; 20(1): 95, 2020 02 27.
Article in English | MEDLINE | ID: mdl-32103724

ABSTRACT

BACKGROUND: We aim to find out the relationship between random blood glucose (RBG), fasting blood glucose (FBG) and in-hospital adverse events in ST-segment elevation acute myocardial infarction (STEMI) patients. We evaluate and compare the predictive value of RBG and FBG on in-hospital adverse events, and give an appropriate cut-off value of RBG and FBG. METHOD: A retrospective study enrolled 958 consecutive AMI patients undergoing emergency coronary angiography at Zhongda Hospital were enrolled from January 1, 2016, to December 31, 2018 was performed. RBG and FBG, baseline data and adverse events were recorded. Major adverse cardiovascular and cerebrovascular events (MACCE) were defined as death, nonfatal recurrent myocardial infarction and stroke. Other adverse events included malignant arrhythmia, cardiac shock and hemorrhage. Patients with RBG > 11.1 mmol/L were divided into elevated RBG group. Patients with FBG > 6.1 mmol/L were divided into elevated FBG group. The incidence of in-hospital adverse events were compared in elevated RBG/FBG group and the control group. ROC curve was used to evaluate the predictive value of RBG and FBG on in-hospital adverse events. RESULT: The incidence of death, hemorrhage, cardiac shock and malignant arrhythmia significantly increases in elevated RBG and FBG group. Binary logistic regression showed that age, hypertension, diabetes, FBG and RBG were independent risk factors for in-hospital adverse events in STEMI patients. The AUC and 95% CI of RBG and FBG in predicting death of AMI patients were 0.789, 0.759~0.816; 0.810, 0.783~0.835, respectively. The cut-off values ​were 13.82 and 7.35 mmol/L. RBG and FBG also had fine predictive value on cardiac shock and malignant arrhythmia, no statistical difference was found in the predictive value on in-hospital adverse events (P = 0.462, P = 0.570, P = 0.694). CONCLUSION: Incidence of in-hospital adverse events significantly increases in AMI patients combined with elevated RBG or FBG. Both RBG and FBG were independent risk factors for in-hospital adverse events, they had good value on predicting in-hospital adverse events and there was no statistical difference in their predictive value.


Subject(s)
Blood Glucose/metabolism , Fasting/blood , Patient Admission , ST Elevation Myocardial Infarction/blood , Aged , Biomarkers/blood , China/epidemiology , Coronary Angiography , Female , Hospital Mortality , Humans , Incidence , Inpatients , Male , Middle Aged , Predictive Value of Tests , Prognosis , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , Stroke/blood , Stroke/mortality , Time Factors
16.
Front Endocrinol (Lausanne) ; 11: 522883, 2020.
Article in English | MEDLINE | ID: mdl-33551987

ABSTRACT

Background and Objectives: Triglyceride-glucose (TyG) is an emerging vital indicator of insulin resistance and is associated with increased risk of T2DM and cardiovascular events. We aimed to explore the TyG index and contrast-induced acute kidney injury (CI-AKI) in patients with type 2 diabetes who underwent coronary angiology. Methods: This study enrolled 928 patients with suspected coronary artery disease who underwent coronary angiology or percutaneous coronary intervention in Zhongda hospital. Patient data were divided into quartiles according to the TyG index: group 1: TyG ≤ 8.62; group 2: 8.629.45. CI-AKI was diagnosed according to the KIDIGO criteria. Demographic data, hematological parameters, coronary angiology data, and medications were all recorded. We calculated the TyG index using the following formula: ln [fasting TG (mg/dL)×FPG (mg/dL)/2]. Results: Patients who developed CI-AKI exhibited significantly higher TyG index levels compared to patients who did not develop CI-AKI. The incidence of CI-AKI sharply increased with increasing TyG. Univariate and multivariate analysis identified TyG as an independent risk factor for CI-AKI. The AUC of the ROC curve was as high as 0.728 when the value of TyG was 8.88. The corresponding sensitivity was as high as 94.9%. Adding the variable TyG to the model for predicting CI-AKI risk further increased the predictive value of the model from 80.4% to 82%. Conclusions: High TyG is closely associated with increased incidence of CI-AKI, demonstrating that TyG is an independent risk factor for CI-AKI. TyG has potentially predictive value for CI-AKI and may play a crucial role in risk stratification in clinical practice.


Subject(s)
Acute Kidney Injury/etiology , Blood Glucose , Contrast Media/adverse effects , Coronary Artery Disease/surgery , Diabetes Mellitus, Type 2/blood , Triglycerides/blood , Acute Kidney Injury/blood , Aged , Aged, 80 and over , China , Coronary Artery Disease/blood , Coronary Artery Disease/complications , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Prospective Studies
18.
Mol Cell Endocrinol ; 500: 110641, 2020 01 15.
Article in English | MEDLINE | ID: mdl-31711985

ABSTRACT

Endothelial cells (ECs) primarily rely on glycolysis for their energy metabolism, and the final product of glycolysis-lactate-is transferred out of cells via monocarboxylate transporter 4 (MCT4). We previously showed that MCT4 downregulation is involved in diabetic endothelial injury. However, the underlying regulatory mechanisms of MCT4 in diabetes remain unclear. This study showed that miR-425-5p was significantly upregulated in diabetic patients and human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG) and interleukin-1ß (IL-1ß). MCT4 was shown to be a direct target gene of miR-425-5p, and miR-425-5p expression led to MCT4 downregulation, lactate accumulation and increased apoptosis in HUVECs. Furthermore, the results indicated that NF-κB signaling activation increased miR-425-5p levels and induced MCT4 downregulation, lactate accumulation and apoptosis in HUVECs. In conclusion, NF-κB/miR-425-5p/MCT4 axis activation plays a crucial role in the EC injury induced by HG and IL-1ß.


Subject(s)
Diabetes Mellitus/genetics , Human Umbilical Vein Endothelial Cells/cytology , MicroRNAs/genetics , Monocarboxylic Acid Transporters/genetics , Muscle Proteins/genetics , NF-kappa B/metabolism , Cell Survival/drug effects , Diabetes Mellitus/metabolism , Down-Regulation , Glucose/adverse effects , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Interleukin-1beta/adverse effects , Lactic Acid/metabolism , Models, Biological , Signal Transduction/drug effects
19.
Cardiovasc Diabetol ; 18(1): 150, 2019 11 13.
Article in English | MEDLINE | ID: mdl-31722708

ABSTRACT

BACKGROUND: Insulin resistance (IR) is considered a pivotal risk factor for cardiometabolic diseases, and the triglyceride-glucose index (TyG index) has emerged as a reliable surrogate marker of IR. Although several recent studies have shown the association of the TyG index with vascular disease, no studies have further investigated the role of the TyG index in acute ST-elevation myocardial infarction (STEMI). The objective of the present study was to evaluate the potential role of the TyG index as a predictor of prognosis in STEMI patients after percutaneous coronary intervention (PCI). METHODS: The study included 1092 STEMI patients who underwent PCI. The patients were divided into 4 quartiles according to TyG index levels. Clinical characteristics, fasting plasma glucose (FPG), triglycerides (TGs), other biochemical parameters, and the incidence of major adverse cardiovascular and cerebral events (MACCEs) during the follow-up period were recorded. The TyG index was calculated using the following formula: ln[fasting TGs (mg/dL) × FPG (mg/dL)/2]. RESULTS: The incidence of MACCEs and all-cause mortality within 30 days, 6 months and 1 year after PCI were higher among STEMI patients with TyG index levels in the highest quartile. The TyG index was significantly associated with an increased risk of MACCEs in STEMI patients within 1 year after PCI, independent of confounding factors, with a value of 1.529 (95% CI 1.001-2.061; P = 0.003) for those in the highest quartile. The area under the curve (AUC) of the TyG index predicting the occurrence of MACCEs in STEMI patients after PCI was 0.685 (95% CI 0.610-0.761; P = 0.001). The results also revealed that Killip class > 1, anaemia, albumin, uric acid, number of stents and left ventricular ejection fraction (LVEF) were independent predictors of MACCEs in STEMI patients after PCI (all P < 0.05). CONCLUSIONS: This study indicated an association between higher TyG index levels and increased risk of MACCEs in STEMI patients for the first time, and the TyG index might be a valid predictor of clinical outcomes in STEMI patients undergoing PCI. Trial Registration ChiCTR1900024577.


Subject(s)
Blood Glucose/metabolism , Insulin Resistance , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/therapy , Triglycerides/blood , Aged , Biomarkers/blood , Cause of Death , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/mortality , Retrospective Studies , Risk Assessment , Risk Factors , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/mortality , Time Factors , Treatment Outcome
20.
Biomed Res Int ; 2019: 8534752, 2019.
Article in English | MEDLINE | ID: mdl-31428649

ABSTRACT

Anaemia and high haemoglobin levels are common in ST elevation myocardial infarction (STEMI) patients, but the effect of the haemoglobin level on the prognosis of STEMI patients remains in dispute. This study aimed to evaluate the prognostic value of the haemoglobin level combined with the CAMI-STEMI score in STEMI patients after percutaneous coronary intervention (PCI). We included 360 STEMI patients who underwent PCI. The patients were divided into 3 groups according to the first haemoglobin value after PCI. Clinical characteristics and the incidence of major adverse cardiovascular and cerebral events (MACCE) during the follow-up period were recorded. The incidence of MACCE in the 3 groups increased with a decrease in the haemoglobin level. Multivariate regression analysis showed that the CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI and that anaemia was an independent predictor of MACCE incidence at 6 months and 1 year after PCI. A high haemoglobin level was an independent predictor of MACCE incidence at 1 year after PCI. The area under receiver operating characteristic curves (AUCs) of the haemoglobin level, CAMI-STEMI score, and haemoglobin level combined with CAMI-STEMI score predicting the occurrence of MACCE in STEMI patients within 30 days after PCI were 0.604, 0.614, and 0.639, respectively. In conclusion, The CAMI-STEMI score was an independent predictor of MACCE incidence at 30 days after PCI. The haemoglobin level combined with the CAMI-STEMI score improved the predictive value of MACCE in STEMI patients within 30 days after PCI. Trial Registration. This trial was a prospective cohort study and registered with ChiCTR-ROC-17011542.


Subject(s)
Cerebrovascular Disorders , Hemoglobins/metabolism , Percutaneous Coronary Intervention , Postoperative Complications , ST Elevation Myocardial Infarction , Aged , Aged, 80 and over , Cerebrovascular Disorders/blood , Cerebrovascular Disorders/epidemiology , Cerebrovascular Disorders/etiology , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Postoperative Complications/blood , Postoperative Complications/epidemiology , Predictive Value of Tests , Prospective Studies , ST Elevation Myocardial Infarction/blood , ST Elevation Myocardial Infarction/epidemiology , ST Elevation Myocardial Infarction/surgery
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