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1.
Am Surg ; 86(8): 976-980, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32762469

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality following orthotopic liver transplant, yet there is no standardized protocol for pre-liver-transplant coronary artery disease assessment. The main objective of this study was to determine the agreement between 2 methods of cardiac risk assessment: dobutamine stress echocardiogram (DSE) and coronary calcium score (CCS) and to determine which test was best able to predict coronary calcification in low-risk patients. METHODS: A retrospective study was performed using the medical records of 436 patients who received cardiac clearance for a liver transplant. A total of 152 patients' medical records were included based on the inclusion of patients who had received both DSE and CCS. A kappa coefficient was calculated to determine the agreement between the DSE and CCS results. In addition, the positive predictive values (PPVs) of both the CCS and DSE along with cardiac catheterization indicating abdominal occlusion were analyzed to compare the accuracy of the 2 tests. RESULTS: It was determined that there was a 12% agreement between DSE results and CCS. It was found that the DSE had a PPV of 56% and the CCS had a PPV of 80%. CONCLUSION: From this data, it was concluded that there was no agreement between the results of the CCS and the DSE. While neither the CCS nor the DSE presents an optimal method of risk assessment, the CCS had a much higher PPV and was therefore determined to be the more accurate test.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Transplante de Fígado , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Biomarcadores/metabolismo , Cálcio/metabolismo , Cateterismo Cardíaco , Regras de Decisão Clínica , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Ecocardiografia sob Estresse , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
2.
Arterioscler Thromb Vasc Biol ; 40(9): 2095-2107, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32757647

RESUMO

OBJECTIVE: Apo (apolipoprotein) CIII mediates the metabolism of triglyceride (TG)-rich lipoproteins. High levels of plasma apoCIII are positively correlated with the plasma TG levels and increase the cardiovascular risk. However, whether apoCIII is directly involved in the development of atherosclerosis has not been fully elucidated. Approach and Results: To examine the possible roles of apoCIII in lipoprotein metabolism and atherosclerosis, we generated apoCIII KO (knockout) rabbits using ZFN (zinc finger nuclease) technique. On a normal standard diet, apoCIII KO rabbits exhibited significantly lower plasma levels of TG than those of WT (wild type) rabbits while total cholesterol and HDL (high-density lipoprotein) cholesterol levels were unchanged. Analysis of lipoproteins isolated by sequential ultracentrifugation revealed that reduced plasma TG levels in KO rabbits were accompanied by prominent reduction of VLDLs (very-low-density lipoproteins) and IDLs (intermediate-density lipoproteins). In addition, KO rabbits showed faster TG clearance rate after intravenous fat load than WT rabbits. On a cholesterol-rich diet, KO rabbits exhibited constantly and significantly lower levels of plasma total cholesterol and TG than WT rabbits, which was caused by a remarkable reduction of ß-VLDLs-the major atherogenic lipoproteins. ß-VLDLs of KO rabbits showed higher uptake by cultured hepatocytes and were cleared faster from the circulation than ß-VLDLs isolated from WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. CONCLUSIONS: These results indicate that apoCIII deficiency facilitates TG-rich lipoprotein catabolism, and therapeutic inhibition of apoCIII expression may become a novel means not only for the treatment of hyperlipidemia but also for atherosclerosis.


Assuntos
Doenças da Aorta/prevenção & controle , Apolipoproteína C-III/deficiência , Aterosclerose/prevenção & controle , Doença da Artéria Coronariana/prevenção & controle , Triglicerídeos/sangue , Animais , Animais Geneticamente Modificados , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Apolipoproteína C-III/genética , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Biomarcadores/sangue , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Feminino , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Lipoproteínas IDL/sangue , Fígado/metabolismo , Masculino , Oxirredução , Placa Aterosclerótica , Coelhos
3.
Gene ; 753: 144805, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32445923

RESUMO

Genomic variants in both ADTRP and TFPI genes are associated with risk of coronary artery disease (CAD). ADTRP regulates TFPI expression and endothelial cell functions involved in the initiation of atherosclerotic CAD. ADTRP also specifies primitive myelopoiesis and definitive hematopoiesis by upregulating TFPI expression. However, the underlying molecular mechanism is unknown. Here we show that transcription factor POU1F1 is the key by which ADTRP regulates TFPI expression. Luciferase reporter assays, chromatin-immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) in combination with analysis of large and small deletions of the TFPI promoter/regulatory region were used to identify the molecular mechanism by which ADTRP regulates TFPI expression. Genetic association was assessed using case-control association analysis and phenome-wide association analysis (PhenGWA). ADTRP regulates TFPI expression at the transcription level in a dose-dependent manner. The ADTRP-response element was localized to a 50 bp region between -806 bp and -756 bp upstream of TFPI transcription start site, which contains a binding site for POU1F1. Deletion of POU1F1-binding site or knockdown of POU1F1 expression abolished ADTRP-mediated transcription of TFPI. ChIP and EMSA demonstrated that POU1F1 binds to the ADTRP response element. Genetic analysis identified significant association between POU1F1 variants and risk of CAD. PhenGWA identified other phenotypic traits associated with the ADTRP-POU1F1-TFPI axis such as lymphocyte count (ADTRP), waist circumference (TFPI), and standing height (POU1F1). These data identify POU1F1 as a transcription factor that regulates TFPI transcription in response to ADTRP, and link POU1F1 variants to risk of CAD for the first time.


Assuntos
Doença da Artéria Coronariana/metabolismo , Lipoproteínas/biossíntese , Proteínas de Membrana/metabolismo , Fator de Transcrição Pit-1/metabolismo , Aterosclerose/genética , Estudos de Casos e Controles , Linhagem Celular , Imunoprecipitação da Cromatina/métodos , Doença da Artéria Coronariana/genética , Bases de Dados Genéticas , Células Endoteliais/metabolismo , Genes Homeobox , Células HeLa , Humanos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Regiões Promotoras Genéticas , Elementos de Resposta , Sítio de Iniciação de Transcrição , Transcrição Genética
4.
BMC Cardiovasc Disord ; 20(1): 101, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32122307

RESUMO

BACKGROUND: This study investigated neutrophil activation and neutrophil-derived extracellular traps formation in coronary artery ectasia. METHODS: We enrolled 90 patients who underwent coronary angiography, and included 30 patients with coronary artery ectasia (CAE), 30 patients with obstructive coronary artery disease (CAD) and 30 patients with normal coronary arteries (CON). Intra-neutrophil mean myeloperoxidase index (MPXI) was determined using an automated blood cell counter (ADVIA2120 Hematology System). Serum concentrations of plasma adhesion molecules, cytokines, and neutrophil-derived extracellular traps were quantified. RESULTS: The intra-neutrophil mean myeloperoxidase index was reduced in CAE patients compared to CAD and CON patients (1.02 ± 3.01, 3.22 ± 3.03, 3.52 ± 4.25, respectively; CAE vs CAD, p = 0.016 and CAE vs CON, p = 0.007). Multiple logistic regression analysis showed that MPXI and dsDNA were independent factors that predicted the presence of CAE. CAE patients had higher levels of plasma adhesion molecules (P-selectin glycoprotein ligand-1, E-selectin, L-selectin) and interleukin 1 beta levels. Neutrophil extracellular trap concentrations were significantly higher in the CAE group compared to CAD and CON patients (284.31(258.33-449.91) ng/mL, 225.12(203.34-257.13) ng/mL, and 247.37(231.04-273.01) ng/mL, respectively; CAE vs CAD, p = 0.000 and CAE vs CON, p = 0.001). CONCLUSIONS: Peripheral neutrophils from CAE patients were activated and neutrophil extracellular traps were elevated in the plasma. IL-1ß and soluble adhesion molecules may be the causal factors for neutrophil activation.


Assuntos
Doença da Artéria Coronariana/metabolismo , Vasos Coronários/metabolismo , Armadilhas Extracelulares/metabolismo , Ativação de Neutrófilo , Neutrófilos/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Moléculas de Adesão Celular/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/imunologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/imunologia , Dilatação Patológica , Armadilhas Extracelulares/imunologia , Feminino , Humanos , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Peroxidase/metabolismo , Estudos Prospectivos
5.
Mol Genet Genomics ; 295(3): 607-619, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32162118

RESUMO

Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) and coronary artery disease (CAD), respectively. Nevertheless, these studies were generally performed for single-trait/disease and failed to assess the pleiotropic role of the identified variants. To identify novel functional loci and the pleiotropic relationship between CAD and T2D, the targeted cFDR analysis on CpG-SNPs was performed by integrating two independent large and multi-centered GWASs with summary statistics of T2D (26,676 cases and 132,532 controls) and CAD (60,801 cases and 123,504 controls). Applying the cFDR significance threshold of 0.05, we observed a pleiotropic enrichment between T2D and CAD by incorporating pleiotropic effects into a conditional analysis framework. We identified 79 novel CpG-SNPs for T2D, 61 novel CpG-SNPs for CAD, and 18 novel pleiotropic loci for both traits. Among these novel CpG-SNPs, 33 of them were annotated as methylation quantitative trait locus (meQTL) in whole blood, and ten of them showed expression QTL (eQTL), meQTL, and metabolic QTL (metaQTL) effects simultaneously. To the best of our knowledge, we performed the first targeted cFDR analysis on CpG-SNPs, and our findings provided novel insights into the shared biological mechanisms and overlapped genetic heritability between T2D and CAD.


Assuntos
Doença da Artéria Coronariana/genética , Ilhas de CpG , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Locos de Características Quantitativas , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Redes Reguladoras de Genes , Pleiotropia Genética , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Mapas de Interação de Proteínas
6.
Arterioscler Thromb Vasc Biol ; 40(4): 986-1000, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102570

RESUMO

OBJECTIVE: Epicardial adipose tissue (EAT) is an active endocrine organ that could contribute to the pathophysiology of coronary artery disease (CAD) through the paracrine release of proatherogenic mediators. Numerous works have analyzed the inflammatory signature of EAT, but scarce informations on its lipidome are available. Our objective was first to study the differences between EAT and subcutaneous adipose tissue (SAT) lipidomes and second to identify the specific untargeted lipidomic signatures of EAT and SAT in CAD. Approach and Results: Subcutaneous and EAT untargeted lipidomic analysis was performed in 25 patients with CAD and 14 patients without CAD and compared with paired plasma lipidomic analysis of isolated VLDL (very low-density lipoprotein) and HDL (high-density lipoprotein). Lipidomics was performed on a C18 column hyphenated to a Q-Exactive plus mass spectrometer, using both positive and negative ionization mode. EAT and SAT had independent lipidomic profile, with 95 lipid species differentially expressed and phosphatidylethanolamine 18:1p/22:6 twenty-fold more expressed in EAT compared with SAT false discovery rate =3×10-4). Patients with CAD exhibited more ceramides (P=0.01), diglycerides (P=0.004; saturated and nonsaturated), monoglycerides (P=0.013) in their EAT than patients without CAD. Conversely, they had lesser unsaturated TG (triglycerides; P=0.02). No difference was observed in the 295 lipid species found in SAT between patients with and without CAD. Fifty-one lipid species were found in common between EAT and plasma lipoproteins. TG 18:0/18:0/18:1 was found positively correlated (r=0.45, P=0.019) in EAT and HDL and in EAT and VLDL (r=0.46, P=0.02). CONCLUSIONS: CAD is associated with specific lipidomic signature of EAT, unlike SAT. Plasma lipoprotein lipidome only partially reflected EAT lipidome.


Assuntos
Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/metabolismo , Pericárdio/metabolismo , Plasmalogênios/metabolismo , Idoso , HDL-Colesterol/sangue , VLDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Gordura Subcutânea/metabolismo
8.
Cardiovasc Diabetol ; 19(1): 24, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093680

RESUMO

BACKGROUND: Obesity, hypertension and prediabetes contribute greatly to coronary artery disease, heart failure and vascular events, and are the leading cause of mortality and morbidity in developed societies. Salt sensitivity exacerbates endothelial dysfunction. Herein, we investigated the effect of chronic glucagon like peptide-1 (GLP-1) receptor activation on the coronary microcirculation and cardiac remodeling in Zucker rats on a high-salt diet (6% NaCl). METHODS: Eight-week old Zucker lean (+/+) and obese (fa/fa) rats were treated with vehicle or liraglutide (LIRA) (0.1 mg/kg/day, s.c.) for 8 weeks. Systolic blood pressure (SBP) was measured using tail-cuff method in conscious rats. Myocardial function was assessed by echocardiography. Synchrotron contrast microangiography was then used to investigate coronary arterial vessel function (vessels 50-350 µm internal diameter) in vivo in anesthetized rats. Myocardial gene and protein expression levels of vasoactive factors, inflammatory, oxidative stress and remodeling markers were determined by real-time PCR and Western blotting. RESULTS: We found that in comparison to the vehicle-treated fa/fa rats, rats treated with LIRA showed significant improvement in acetylcholine-mediated vasodilation in the small arteries and arterioles (< 150 µm diameter). Neither soluble guanylyl cyclase or endothelial NO synthase (eNOS) mRNA levels or total eNOS protein expression in the myocardium were significantly altered by LIRA. However, LIRA downregulated Nox-1 mRNA (p = 0.030) and reduced ET-1 protein (p = 0.044) expression. LIRA significantly attenuated the expressions of proinflammatory and profibrotic associated biomarkers (NF-κB, CD68, IL-1ß, TGF-ß1, osteopontin) and nitrotyrosine in comparison to fa/fa-Veh rats, but did not attenuate perivascular fibrosis appreciably. CONCLUSIONS: In a rat model of metabolic syndrome, chronic LIRA treatment improved the capacity for NO-mediated dilation throughout the coronary macro and microcirculations and partially normalized myocardial remodeling independent of changes in body mass or blood glucose.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Circulação Coronária/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Resistência à Insulina , Liraglutida/farmacologia , Microcirculação/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Modelos Animais de Doenças , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipertensão/etiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Óxido Nítrico/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Obesidade/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Zucker , Cloreto de Sódio na Dieta , Remodelação Ventricular/efeitos dos fármacos
9.
Dis Markers ; 2020: 7190828, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076463

RESUMO

Aims: Fibrin formation and histidine-rich glycoprotein (HRG) are involved in primary hemostasis and wound healing. Little is known regarding the relationship of clot characteristics, bleeding time, and wound healing. Methods and Results: We studied 154 patients with coronary artery disease (CAD) and 154 subjects free of CAD matched for age, obesity, and current smoking. We evaluated bleeding time (BT) using standardized skin incisions on a forearm, along with plasma clot permeability (K s), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower K s), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower p < 0.001). After adjusting for potential confounders, K s), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower n = 79, 25.6%) was independently predicted by both short and prolonged BT in CAD cases (OR 21.87, 95% CI 7.41-64.55 and OR 10.17, 95% CI 2.88-35.97) and controls (OR 5.94, 95% CI 2.29-15.41 and OR 14.76, 95% CI 4.29-50.77, respectively). Conclusions: The study shows that plasma fibrin clot density and HRG may influence BT and that appropriate skin wound healing is associated with medium BT. Translational Perspective. Elucidation of the complex relationships between plasma fibrin clot phenotype and wound healing might have important practical implications.


Assuntos
Doença da Artéria Coronariana/metabolismo , Fibrina/metabolismo , Proteínas/metabolismo , Idoso , Tempo de Sangramento , Estudos de Casos e Controles , Feminino , Tempo de Lise do Coágulo de Fibrina , Humanos , Masculino , Pessoa de Meia-Idade , Cicatrização
10.
EBioMedicine ; 52: 102649, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32062353

RESUMO

Host-microbiota interactions involving inflammatory and metabolic pathways have been linked to the pathogenesis of multiple immune-mediated diseases and metabolic conditions like diabetes and obesity. Accumulating evidence suggests that alterations in the gut microbiome could play a role in cardiovascular disease. This review focuses on recent advances in our understanding of the interplay between diet, gut microbiota and cardiovascular disease, with emphasis on heart failure and coronary artery disease. Whereas much of the literature has focused on the circulating levels of the diet- and microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), several recent sequencing-based studies have demonstrated compositional and functional alterations in the gut microbiomes in both diseases. Some microbiota characteristics are consistent across several study cohorts, such as a decreased abundance of microbes with capacity for producing butyrate. However, the published gut microbiota studies generally lack essential covariates like diet and clinical data, are too small to capture the substantial variation in the gut microbiome, and lack parallel plasma samples, limiting the ability to translate the functional capacity of the gut microbiomes to actual function reflected by circulating microbiota-related metabolites. This review attempts to give directions for future studies in order to demonstrate clinical utility of the gut-heart axis.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Animais , Butiratos/metabolismo , Dieta , Disbiose/metabolismo , Ácidos Graxos Voláteis/biossíntese , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/metabolismo , Metagenoma , Metagenômica , Transdução de Sinais
11.
Vascul Pharmacol ; 127: 106660, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32070767

RESUMO

Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis especially in coronary arteries. Berberine (BBR) shows several beneficial effects on cardiovascular system. The present study is to investigate whether BBR exerts protective effect against KD-induced damage of human coronary artery endothelial cell (HCAECs) and the underlying mechanisms. HCAECs exposed to medium with 15% serum from KD patients or healthy volunteers for 24 h. Stimulated HCAECs were treated with vehicle (without BBR) and BBR (20 µM) for 24 h, the cell apoptosis, cell cycle, induction of intracellular reactive oxygen species (ROS) and protein expression were examined by flow cytometry and western blot. The KD-induced differentially expressed proteins in HCAECs were determined by quantitative proteomics. BBR inhibited HCAECs from apoptosis and arrested cell cycle at G0/G1 stage. BBR protected HCAECs from injury by inhibiting expression of THBD, vWF and EDN1. Bioinformatics analysis suggested that the oxidative and ER stress were involved in KD-induced damage in HCAECs. ROS production and the protein expression of ATF4, p-EIF2α, p-PERK, XBP1, p-IRE1, HSP90B1, HSPG2, DNAJC3, P4HB and VCP were increased by serum from KD patients and decreased by BBR treatment. BBR exerts its protective effects on KD-induced damage of HCAECs through its inhibitory effects on oxidative and ER stress indicating BBR as a therapeutic candidate for KD.


Assuntos
Antioxidantes/farmacologia , Berberina/farmacologia , Doença da Artéria Coronariana/prevenção & controle , Vasos Coronários/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Estudos de Casos e Controles , Células Cultivadas , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/metabolismo , Síndrome de Linfonodos Mucocutâneos/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
JACC Cardiovasc Interv ; 13(1): 1-19, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31918927

RESUMO

Despite optimal combination of guideline-directed anti-ischemic therapies and myocardial revascularization, a substantial proportion of patients with stable coronary artery disease continues to experience disabling symptoms and is often referred as "no-option." The appraisal of the pathways linking ischemia to symptom perception indicates a complex model of heart-brain interactions in the generation of the subjective anginal experience and inspired novel approaches that may be clinically effective in alleviating the angina burden of this population. Conversely, the prevailing ischemia-centered view of angina, with the focus on traditional myocardial revascularization as the sole option to address ischemia on top of medical therapy, hinders the experimental characterization and broad-scale clinical implementation of strongly needed therapeutic options. The interventionist, often the first physician to establish the diagnosis of refractory angina pectoris (RAP) following coronary angiography, should be aware of the numerous emerging technologies with the potential to improve quality of life in the growing population of RAP patients. This review describes the current landscape and the future perspectives on nonpharmacological treatment technologies for patients with RAP, with a view on the underlying physiopathological rationale and current clinical evidence.


Assuntos
Angina Pectoris/terapia , Doença da Artéria Coronariana/terapia , Contrapulsação , Terapia por Estimulação Elétrica , Tratamento por Ondas de Choque Extracorpóreas , Terapia Genética , Coração/inervação , Terapia a Laser , Transplante de Células-Tronco , Angina Pectoris/genética , Angina Pectoris/metabolismo , Angina Pectoris/fisiopatologia , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Contrapulsação/efeitos adversos , Terapia por Estimulação Elétrica/efeitos adversos , Metabolismo Energético , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Terapia Genética/efeitos adversos , Humanos , Terapia a Laser/efeitos adversos , Miocárdio/metabolismo , Transplante de Células-Tronco/efeitos adversos , Resultado do Tratamento
13.
Int J Mol Sci ; 21(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948131

RESUMO

Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarkers of ROS-related cardiac diseases, including myocardial infarction, hypertrophy, ischemia/reperfusion, and heart failure, such as miRNA-499, miRNA-199, miRNA-21, miRNA-144, miRNA-208a, miRNA-34a, etc. On the other hand, a lot of studies are aimed at using miRNAs for therapeutic purposes. This review points to the need for studying the role of redox-sensitive miRNAs, to identify more effective biomarkers and develop better therapeutic targets for oxidative-stress-related heart diseases.


Assuntos
Cardiomegalia/metabolismo , Doença da Artéria Coronariana/metabolismo , Insuficiência Cardíaca/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo/genética , Animais , Cardiomegalia/genética , Doença da Artéria Coronariana/genética , Insuficiência Cardíaca/genética , Humanos , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/genética , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
14.
Clin Chim Acta ; 503: 136-144, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972150

RESUMO

BACKGROUND: Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". OBJECTIVE: To clarify the cross-sectional relationship between CUC and coronary plaque properties. METHODS: We enrolled 135 patients to measure CUC and assess the morphological features of angiographic stenosis by optical coherence tomography (OCT). We estimated the extent of the lipid-rich plaque by multiplying the mean lipid arc by lipid length (lipid index). The extent of the OCT-detected macrophage accumulation in the target plaque was semi-quantitatively estimated using a grading system. RESULTS: Lipid-rich plaque lesions were identified in 125 patients (92.6%). CUC was inversely associated with the lipid index (R = -0.348, P < 0.0001). In addition, CUC was also inversely associated with macrophage score (R = -0.327, P < 0.0001). Conversely, neither circulating levels of HDL cholesterol nor apoA1 showed a similar relationship. CONCLUSIONS: We demonstrated that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation, suggesting that CUC could be useful for cardiovascular risk stratification.


Assuntos
Colesterol/farmacocinética , Doença da Artéria Coronariana/patologia , Lipoproteínas HDL/fisiologia , Placa Aterosclerótica/patologia , Idoso , Apolipoproteína A-I , HDL-Colesterol , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Lipídeos/análise , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo , Tomografia de Coerência Óptica/métodos
15.
Int J Mol Sci ; 21(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979197

RESUMO

The aim of our study was to examine the regulation of triacylglycerols (TG) metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis. Adipose triglyceride lipase (ATGL) is the major TG-hydrolase. The enzyme is activated by a protein called comparative gene identification 58 (CGI-58) and inhibited by a protein called G0/G1 switch protein 2 (G0S2). Samples of the right atrial appendage and perivascular adipose tissue were obtained from two groups of patients: 1-with multivessel coronary artery disease qualified for coronary artery bypass grafting (CAD), 2-patients with no atherosclerosis qualified for a valve replacement (NCAD). The mRNA and protein analysis of ATGL, HSL, CGI-58, G0S2, FABP4, FAT/CD36, LPL, ß-HAD, CS, COX4/1, FAS, SREBP-1c, GPAT1, COX-2, 15-LO, and NFκß were determined by using real-time PCR and Western Blot. The level of lipids (i.e., TG, diacylglycerol (DG), and FFA) was examined by GLC. We demonstrated that in myocardium coronary atherosclerosis increases only the transcript level of G0S2 and FABP4. Most importantly, ATGL, ß-HAD, and COX4/1 protein expression was reduced and it was accompanied by over double the elevation in TG content in the CAD group. The fatty acid synthesis and their cellular uptake were stable in the myocardium of patients with CAD. Additionally, the expression of proteins contributing to inflammation was increased in the myocardium of patients with coronary stenosis. Finally, in the perivascular adipose tissue, the mRNA of G0S2 was elevated, whereas the protein content of FABP-4 was increased and for COX4/1 diminished. These data suggest that a reduction in ATGL protein expression leads to myocardial steatosis in patients with CAD.


Assuntos
Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/metabolismo , Expressão Gênica/genética , Coração/fisiologia , Lipólise/genética , Miocárdio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Humanos , Lipase/metabolismo , Metabolismo dos Lipídeos/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Triglicerídeos/metabolismo
16.
Int Heart J ; 61(1): 115-120, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956140

RESUMO

Coronary collateral circulation (CCC) plays a crucial role in myocardial blood supply, especially for ischemic myocardium. Previous study has shown that neuregulin-1 is a prominent angiogenic factor in diabetic cardiomyopathy, whereas the relationship between neuregulin-1 and CCC has not been investigated. Thus, we aimed to investigate relationship between circulating neuregulin-1 levels and CCC in stable coronary artery disease patients.Coronary artery disease patients with a stenosis of ≥ 90% as evidenced by coronary angiography were included in our study. According to the Rentrop-Cohen classification, coronary collateral degree was graded as 1 to 4. Patients with collateral degree grade 0 or 1 were enrolled in poor CCC group, whereas patients with grade 2 or 3 were enrolled in good CCC group.Plasma neuregulin-1 level was significantly increased in good collateral group and positively related to Rentrop grade (P < 0.01). Multivariate regression analysis and ROC (receiver operating characteristic curve) revealed that plasma neuregulin-1 could predict CCC status effectively.Increased plasma neuregulin-1 level was related to better CCC in patients with coronary artery disease. Neuregulin-1 was an independent and reliable predictor for good coronary collateral development and provided a potential therapeutic strategy to reduce myocardial ischemia injury.


Assuntos
Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Neuregulina-1/sangue , Idoso , Circulação Colateral , Angiografia Coronária , Doença da Artéria Coronariana/metabolismo , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Regulação para Cima
17.
Life Sci ; 245: 117338, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31981630

RESUMO

Secreted frizzled-related protein 5 (Sfrp5) primarily acts in combination with wingless-type family member 5a (Wnt5a), to inhibits chronic inflammation and repress atherosclerosis and other metabolic disorders. Epicardial adipose tissue (EAT), surrounding the heart and coronary arteries, has been found to be highly related to the progression of coronary artery disease through adipokines production. However, little is known about EAT-derived Sfrp5 and Wnt5a in humans. We aimed to investigate whether the EAT-derived Sfrp5/Wnt5a levels are altered in patients with CAD. Fifty-eight patients with CAD and 29 patients without CAD who underwent cardiac surgery were enrolled. Serum samples and paired adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected, and Sfrp5 and Wnt5a levels were detected. Correlation and multivariate regression analyses were performed to determine the relationship between Sfrp5/Wnt5a expression and CAD and other clinical risk factors. According to the results, the CAD group had lower Sfrp5 and higher Wnt5a levels in EAT and serum (all p < 0.05). Serum Sfrp5 levels were significantly lower in CAD patients with impaired myocardial function. EAT Sfrp5 mRNA levels and serum Sfrp5 levels were both negatively associated with the presence of CAD, after adjustment for known biomarkers, EAT mRNA and serum Wnt5a levels correlated positively with the presence of CAD. Thus, we concluded that low Sfrp5 and high Wnt5a levels are associated with the presence of CAD, independent of other conventional risk factors.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/metabolismo , Pericárdio/metabolismo , Proteína Wnt-5a/metabolismo , Tecido Adiposo/patologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericárdio/patologia , Reação em Cadeia da Polimerase em Tempo Real
18.
Clin Sci (Lond) ; 134(2): 273-287, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31957803

RESUMO

The current main treatment for coronary artery disease (CAD) is to reduce low-density lipoprotein cholesterol (LDL-C) by statins, which could decrease the incidence of major adverse cardiovascular events (MACEs) by 30%. However, many residual risks still remain. To clarify the mechanism involved, we studied patients with acute myocardial infarction (AMI) with low LDL-C levels. Lymphocytes were isolated, and it was found that despite no difference in plasma LDL-C level, the lymphocyte cholesterol content was higher in AMI patient than those in non-CAD patients; thus, the decrease in intracellular cholesterol content was inconsistent with that in the plasma. Additionally, [3H]-cholesterol efflux rates were lower and mRNA levels of the inflammatory factors tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) higher in AMI lymphocytes. It was found that sulphotransferase 2B1b (SULT2B1b) expression was higher in AMI lymphocytes. Further research using Jurkat T lymphocytes confirmed that SULT2B1b knockdown increased cholesterol efflux capacity and decreased mRNA levels of TNF-α and IFN-γ by increasing liver X receptor (LXR)-ß levels. Furthermore, the degree of CpG island methylation in the SULT2B1b promoter was reduced in cells from AMI patients. In conclusion, SULT2B1b up-regulation due to hypomethylation of its promoter promotes cholesterol accumulation and inflammation by inhibiting LXR-ß in lymphocytes of AMI patients with low LDL-C levels. Therefore, reducing intracellular cholesterol is also important as plasma cholesterol levels. Therapeutic approaches to decrease SULT2B1b expression might be potentially beneficial for CAD prevention by decreasing intracellular cholesterol.


Assuntos
Colesterol/metabolismo , Interferon gama/metabolismo , Linfócitos/metabolismo , Sulfotransferases/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Transporte Biológico , Colesterol/sangue , LDL-Colesterol/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/prevenção & controle , Metilação de DNA , Humanos , Mediadores da Inflamação/metabolismo , Interferon gama/genética , Células Jurkat , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/prevenção & controle , Regiões Promotoras Genéticas/genética , Sulfotransferases/genética , Fator de Necrose Tumoral alfa/genética
19.
Angiology ; 71(4): 360-365, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31888345

RESUMO

Several laboratory parameters have been used to assess inflammatory process and determine cardiovascular risk. The C-reactive protein to albumin ratio (CAR) is a novel marker of inflammation and its clinical importance has not been clearly elucidated in coronary artery disease (CAD). We compared the diagnostic value of CAR with other inflammatory parameters in detecting significant CAD. Patients (n = 421) with stable angina pectoris who underwent coronary angiography for the suspected CAD were included. Neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio, uric acid, monocyte to high-density cholesterol (HDL-C) ratio, mean platelet volume to lymphocyte ratio (MPVLR), and platelet to mean corpuscular volume (MCV) ratio were measured. Patients with significant CAD had a significantly higher NLR (P = .043), MLR (P = .004), uric acid (P < .001), monocyte to HDL-C ratio (P = .004), and CAR (P < .001) compared to patients without significant CAD. However, MPVLR and platelet to MCV ratio weren't different between 2 groups. The area under the curve (AUC) of CAR was the highest AUC among all inflammatory parameters for predicting significant CAD. Multivariate analysis showed that age (odds ratio [OR]: 1.046, 95% confidence interval [CI], 1.020-1.072, P < .001) and CAR (OR: 1.175, 95% CI, 1.126-1.226, P < .001) were the only independent predictors of significant CAD. In conclusion, CAR had the strongest diagnostic value in detecting significant CAD among the inflammatory parameters evaluated in this study.


Assuntos
Albuminas/metabolismo , Angina Estável/diagnóstico , Angina Estável/metabolismo , Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/metabolismo , Biomarcadores/metabolismo , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
20.
Arterioscler Thromb Vasc Biol ; 40(1): 20-33, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31722535

RESUMO

Macrophages play a central role in the development of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary artery disease, peripheral artery disease, cerebrovascular disease, and aortic atherosclerosis. In each vascular bed, macrophages contribute to the maintenance of the local inflammatory response, propagate plaque development, and promote thrombosis. These central roles, coupled with their plasticity, makes macrophages attractive therapeutic targets in stemming the development of and stabilizing existing atherosclerosis. In the context of ASCVD, classically activated M1 macrophages initiate and sustain inflammation, and alternatively activated M2 macrophages resolve inflammation. However, this classification is now considered an oversimplification, and a greater understanding of plaque macrophage physiology in ASCVD is required to aid in the development of therapeutics to promote ASCVD regression. Reviewed herein are the macrophage phenotypes and molecular regulators characteristic of ASCVD regression, and the current murine models of ASCVD regression.


Assuntos
Aterosclerose/imunologia , Doença da Artéria Coronariana/imunologia , Ativação de Macrófagos , Macrófagos/microbiologia , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Progressão da Doença , Humanos , Contagem de Leucócitos , Macrófagos/metabolismo , Macrófagos/patologia , Fenótipo , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia
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