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1.
Int Heart J ; 61(1): 29-38, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956139

RESUMO

Low-circulating levels of adiponectin (ADPN) are associated with obesity, diabetes mellitus, and coronary artery disease. On the contrary, some studies have demonstrated a link between relatively high levels of plasma ADPN and heart failure, atrial fibrillation, and adverse outcome. However, little is known about the relationship between ADPN level and prolonged QT interval. The aim of this study was to investigate the association between plasma ADPN levels and prolonged QT interval in patients with stable angina.In this retrospective study, because the diverse disease severity and condition of the study population may have affected the results, we chose individuals with stable angina. Plasma ADPN concentrations were measured using enzyme-linked immunosorbent assays. A 12-lead ECG recording was obtained from each patient.We enrolled 479 stable-angina patients. Patients with an abnormal corrected QT (QTc) interval had higher median plasma ADPN levels than those with normal QTc intervals. Age- and sex-adjusted ADPN levels were positively associated with heart rate, QTc interval, left ventricular mass index, and creatinine but negatively associated with left ventricular ejection fraction, waist circumference, current smoking, total cholesterol, triglycerides, low-density lipoprotein cholesterol, albumin, and estimated glomerular filtration rate. A multiple logistic regression analysis revealed ADPN as an independent association factor for abnormal QTc interval. Increasing concentrations of sex-specific ADPN were independently and significantly associated with abnormal QTc interval, even after full adjustment of known biomarkers.Our results indicate that ADPN may play a role in the pathogenesis of abnormal QTc interval in patients with stable angina.


Assuntos
Adiponectina/sangue , Angina Estável/fisiopatologia , Biomarcadores/sangue , Síndrome do QT Longo/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Angina Estável/metabolismo , Eletrocardiografia , Feminino , Humanos , Modelos Logísticos , Síndrome do QT Longo/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
2.
Medicine (Baltimore) ; 98(41): e17536, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593130

RESUMO

Recently, the monocyte count to high-density lipoprotein cholesterol ratio (MHR) was found to be associated with the SYNTAX score in patients with both stable coronary artery disease (CAD) and acute coronary syndrome (ACS). The MHR was significantly higher in male patients. However, the sex-specific association of MHR with SYNTAX score in stable CAD was not well explored. Thus, the present study aimed to investigate the association of MHR and presence and severity of CAD evaluated by coronary angiography and the SYNTAX score in males and females.In total, 873 patients who received selective coronary angiography between March 2017 and July 2018 were included in the present study. Patients were divided into 3 groups according to MHR tertiles. The MHR was calculated by dividing the monocyte count by the high-density lipoprotein cholesterol level. CAD was defined as at least 50% diameter stenosis of a major coronary artery, including the right coronary, left main coronary, left anterior descending, and left circumflex arteries. The SYNTAX score was calculated by 2 experienced interventional cardiologists. SYNTAX score ≥23 was defined as a high SYNTAX score.Males showed a significantly higher MHR (12.2 [8.9-15.5] vs 9.3 [6.2-12.1], P < .001), accompanied by a higher prevalence of CAD (68.1% vs 53.4%, P < .001). Male sex remained an independent predictor of elevated MHR after correction for confounding factors (adjusted odds ratio [OR] 3.102, P = .001). The association between MHR and SYNTAX score was confirmed only in male stable patients with CAD (r = 0.113, P = .036). Multivariate logistic regression analysis showed that MHR was an independent predictor of SYNTAX score ≥23 only in male patients with CAD. The receiver-operating characteristic curve showed a predictive value of MHR for high SYNTAX score only in males.A higher MHR in males and a positive correlation of MHR with SYNTAX score were observed only in male stable patients with CAD. Such an easily obtained index may help interventional cardiologists detect high-risk patients before coronary catheterization, but its application may be restricted to males.


Assuntos
HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Contagem de Leucócitos/métodos , Monócitos/citologia , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/metabolismo , Idoso , Angina Estável/sangue , Angina Estável/epidemiologia , Angina Estável/metabolismo , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Índice de Gravidade de Doença , Fatores Sexuais
3.
Life Sci ; 232: 116547, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176780

RESUMO

AIMS: This study aims to investigate the value of the expression of miR-208, miR-494, miR-499 and miR-1303 in the early diagnosis of acute myocardial infarction (AMI). MAIN METHODS: Patients were divided into two groups: AMI group (n = 41), and Stable angina pectoris (SAP) group (n = 32). Peripheral venous blood was sampled from these patients at the time of admission (T0), 6 h after onset (T6) and 12 h after onset (T12), while blood was sampled once from healthy subjects who underwent physical examination in the same time period (control group, n = 10). The expression of miR-208, miR-494, miR-499 and miR-1303 in serum were detected by real-time quantitative polymerase chain reaction (qRT-PCR), and differences in miRNA expression among these three groups of patients were analyzed. KEY FINDINGS: Serum miR-208, miR-494, miR-499 and miR-1303 expression levels at different time points were significantly higher in the AMI group than in the SAP group and control group. The differences among these groups were statistically significant (P < 0.05), while the difference between the SAP group and control group was not statistically significant (P > 0.05). Variation trend: The miRNA levels above began to increase at T0 in the AMI group, the peak levels of miR-208, miR-494 and miR-499 appeared before T12, and the peak level of miR-1303 appeared between T6 and T12, or after T12. SIGNIFICANCE: miR-208, miR-494, miR-499 and miR-1303 were not superior to hs-cTnI as myocardial markers in the diagnosis of early acute myocardial infarction.


Assuntos
MicroRNAs/genética , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/genética , Idoso , Angina Estável/genética , Angina Estável/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , MicroRNAs/análise , Pessoa de Meia-Idade , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma/genética , Troponina I/análise , Troponina I/sangue , Troponina T/análise , Troponina T/sangue
4.
Medicine (Baltimore) ; 98(7): e14309, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762730

RESUMO

Coronary heart disease (CHD), one of the leading causes of death in the world, is a complex metabolic disorder due to genetic and environmental interactions. The potential mechanisms and diagnostic biomarkers for different types of coronary heart disease remain unclear. Metabolomics is increasingly considered to be a promising technology with the potential to identify metabolomic features in an attempt to distinguish the different stages of CHD.We aimed to investigate serum metabolite profiling between CHD patients and normal coronary artery (NCA) subjects and identify metabolic biomarkers associated with CHD progression in an ethnic Hakka population in southern China.Using a novel targeted metabolomics approach, we explored the metabolic characteristics of CHD patients. Blood samples from 302 patients with CHD and 59 NCA subjects were collected that analyses using targeted liquid-chromatography coupled with tandem mass spectrometry (LC-MS).A total of 361 blood samples were determined using targeted LC-MS. Plasma concentrations for trimetlylamine oxide (TMAO), choline, creatinine, and carnitine were significantly higher in patients with CHD compared to the NCA cohort. Further, we observed that the concentration of the 4 metabolites were higher than that of the NCA group in any group of CHD, which including acute myocardial infarction (AMI), unstable angina (UA), and stable angina (SA). In addition, the diagnostic model was constructed based on the metabolites identified and the ROC curve of the NCA subjects and CHD patients were performed. For choline and creatinine, the AUCs ranged from 0.720 to 0.733. For TMAO and carnitine, the AUCs ranged from 0.568 to 0.600.In conclusion, the current study illustrates the distribution of 4 metabolites between CHD patients and NCA subjects. Metabolomics analysis may yield novel predictive biomarkers that will potentially provide value for clinical diagnosis of CHD.


Assuntos
Angina Estável/metabolismo , Metabolômica/métodos , Infarto do Miocárdio/metabolismo , Idoso , Angina Estável/sangue , Angina Estável/diagnóstico , Angina Instável/metabolismo , Biomarcadores , Carnitina/biossíntese , China , Colina/biossíntese , Cromatografia Líquida , Creatinina/sangue , Feminino , Humanos , Masculino , Metilaminas/sangue , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
5.
Biomed Pharmacother ; 109: 690-700, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551521

RESUMO

Chronic stable angina (CSA) presents as a complication of coronary heart disease, leading to a high incidence and mortality rate worldwide. Dantonic® or Compound Danshen Dripping Pills (CDDP) is a well-known traditional Chinese medicine used for the treatment of myocardial ischemic diseases, such as angina pectoris (AP), myocardial infarction, and sudden death. Dantonic® has been extensively utilized in clinical practice in China for more than 14 years and has proved to be an effective therapy for the treatment of many myocardial ischemic diseases since its approval by CFDA in 1994. Clinical studies in China have shown that Dantonic® is an effective and safe drug for the treatment of angina pectoris manifested with ameliorating anginal symptoms and showing few adverse effects. Nevertheless, the mechanism of Dantonic® for the treatment of angina has been underestimated. Therefore, in this review, we mainly focus on discussing the pharmacological mechanism of action (MoA) of Dantonic® for the treatment of CSA, including the promotion of coronary microcirculation, the optimization of myocardial energy metabolism, and the inhibition of platelet aggregation.


Assuntos
Angina Estável/tratamento farmacológico , Angina Estável/fisiopatologia , Cardiotônicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Angina Estável/metabolismo , Animais , Cardiotônicos/farmacologia , China , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Humanos , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Resultado do Tratamento
6.
Acta Pharmacol Sin ; 39(6): 952-960, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29417948

RESUMO

Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. All of the 5 Danshen-based preparations were effective in treating stable angina with clinical improvement rates of 72.4%-91.6% and electrocardiogram (ECG) improvement rates of 54.5%-71.6%. According to both clinical improvement and ECG improvement, the 5 Danshen-based preparations were ranked as follows: Danhong injection > Salvianolate injection > STS injection > compound Danshen injection > Danshen injection. There were no significant differences among the safety profiles of the 5 Danshen preparations. The meta-analysis results were further examined using a network pharmacology approach and functional enrichment analysis, which revealed that Danshen and Danhong injections affected 4 and 15 signaling pathways, respectively, and that the 4 signaling pathways affected by Danshen were a subset of those influenced by Danhong. Therefore, Danhong injection affected some unique signaling pathways that might regulate lipoprotein metabolism, oxidation, and inflammation, and protect vascular endothelia, reflecting the multi-component and multi-target characteristics of this traditional formula and its strengths in treating complex diseases.


Assuntos
Angina Estável/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Salvia miltiorrhiza , Transdução de Sinais/efeitos dos fármacos , Biologia de Sistemas/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Estável/diagnóstico , Angina Estável/metabolismo , Angina Estável/fisiopatologia , Medicamentos de Ervas Chinesas/efeitos adversos , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Resultado do Tratamento
7.
Dis Markers ; 2017: 7909407, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259350

RESUMO

Regulatory T cells (Tregs) play an essential role in acute coronary syndrome (ACS). However, there is debate about which Treg subsets are truly critical to ACS. Helios, a transcription factor, was recently reported to be a bona fide marker for natural Tregs or activated Tregs with a suppression function, but little is known about its role in ACS. We therefore examined Helios+ Tregs in patients with ACS, patients with stable angina, and control subjects. 73 patients with ACS, 30 patients with stable angina, and 48 control subjects were enrolled. The frequencies and estimated absolute numbers of different Treg subsets in peripheral blood were measured by flow cytometry. Plasma cytokine level was measured by ELISA. The mRNA expression of Foxp3 and Helios in purified CD4+ T cells was determined by RT-PCR. Helios+ Tregs was decreased significantly in patients with ACS. The frequency and estimated absolute numbers of CD4+Foxp3+Helios+ Tregs were negatively correlated with IL-6 and positively correlated with circulating level of TGF-beta1 and HDL-C. The mRNA expression of Foxp3 and Helios was decreased in CD4+ T cells from patients with ACS. In summary, Helios+ Tregs was downregulated in patients with ACS and may play a role in ACS.


Assuntos
Síndrome Coronariana Aguda/sangue , Angina Estável/sangue , Fator de Transcrição Ikaros/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/metabolismo , Angina Estável/genética , Angina Estável/metabolismo , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Humanos , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo , Masculino , Pessoa de Meia-Idade
8.
PLoS One ; 12(6): e0180303, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28665970

RESUMO

BACKGROUND: The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. METHODS: We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. RESULTS: Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 µm [58 to 92 µm] vs. 152 µm [115 to 218 µm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). CONCLUSION: OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries.


Assuntos
Colesterol/metabolismo , Vasos Coronários/patologia , Imagem Óptica/métodos , Placa Aterosclerótica/patologia , Idoso , Angina Estável/metabolismo , Angina Estável/patologia , Vasos Coronários/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/metabolismo
9.
Redox Biol ; 12: 899-907, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28472752

RESUMO

Coronary heart disease (CHD) is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA), myocardial infarction (MI), and healthy control (HC). Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL) metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL), and downstream metabolites derived from polyunsaturated fatty acids (PUFAs), such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO) pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC.


Assuntos
Angina Estável/metabolismo , Peroxidação de Lipídeos , Metabolômica/métodos , Infarto do Miocárdio/metabolismo , Adulto , Angina Estável/sangue , Angina Estável/patologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Glicerofosfolipídeos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Estresse Oxidativo , Plasma/química
10.
Clin Chim Acta ; 471: 68-75, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28501389

RESUMO

The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158m/z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD.


Assuntos
Angina Estável/diagnóstico , Angina Estável/metabolismo , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/metabolismo , Proteômica , Angina Estável/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Prognóstico
11.
Cell Transplant ; 26(2): 327-337, 2017 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-27938493

RESUMO

CD34+ progenitor cells are growing in use for vascular repair. However, in diabetic individuals with cardiovascular diseases, these cells have dysfunctional engraftment capabilities, which compromise their use for autologous cell therapy. The thrombospondin-1-derived peptide RFYVVMWK has previously been reported to stimulate cell adhesiveness through CD47 and integrin activation pathways. Our aim was to test whether RFYVVMWK preconditioning could modulate CD34+ cell phenotype and enhance its proadhesive properties in diabetic patients. Peripheral blood mononuclear CD34+ cells isolated from 40 atherosclerotic patients with type 2 diabetes (T2D; n = 20) or without (non-T2D; n = 20) were preconditioned with 30 µM RFYVVMWK or truncated peptide RFYVVM. CD34+ cell adhesion was assessed on a vitronectin-collagen matrix and on TNF-α or IL-1ß-stimulated HUVEC monolayers. Adhesion receptors, platelet/CD34+ cell conjugates, and cell viability were analyzed by flow cytometry and confocal microscopy. RFYVVMWK increased the adhesion of T2D CD34+ cells by eightfold to the vitronectin-collagen matrix (p < 0.001) corresponding to a threefold increase compared to unstimulated non-T2D CD34+ cells. The peptide induced the formation of platelet/CD34+ conjugates and increased the expression of TSP-1, CD29, CD51/CD61, and CD62P in both T2D and non-T2D cells. However, RFYVVMWK treatment did not affect the viability/apoptosis of CD34+ progenitor cells. In conclusion, priming CD34+ cells with RFYVVMWK may enhance their vascular engraftment during autologous proangiogenic cell therapy.


Assuntos
Antígenos CD34/metabolismo , Aterosclerose/imunologia , Aterosclerose/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Leucócitos Mononucleares/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Trombospondina 1/química , Síndrome Coronariana Aguda/imunologia , Síndrome Coronariana Aguda/metabolismo , Idoso , Angina Estável/imunologia , Angina Estável/metabolismo , Adesão Celular/fisiologia , Células Cultivadas , Colágeno/metabolismo , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/química , Inibidores da Agregação de Plaquetas/farmacologia , Vitronectina/metabolismo
12.
Cardiovasc Drugs Ther ; 30(4): 379-391, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27497930

RESUMO

Despite continuous advances in myocardial revascularization procedures and intracoronary devices, patients with ischemic heart disease (IHD) still experience worse prognosis and poor quality of life (QoL). Indeed, chronic stable angina (CSA) is a common disease with a large burden on healthcare costs. Traditionally, CSA is interpreted as episodes of reversible myocardial ischemia related to the presence of stable coronary artery plaque causing myocardial demand/supply mismatch when myocardial oxygen consumption increases. Accordingly, revascularization procedures are performed with the aim to remove the flow limiting stenosis, whereas traditional medical therapy (hemodynamic agents) aims at reducing myocardial oxygen demands. However, although effective, none of these treatment strategies or their combination is either able to confer symptomatic relief in all patients, nor to reduce mortality. Failure to significantly improve QoL and prognosis may be attributed at least in part to this "restrictive" understanding of IHD. Despite for many years myocardial metabolic derangement has been overlooked, recently it has gained increased attention with the development of new pharmacological agents (metabolic modulators) able to influence myocardial substrate selection and utilization thus improving cardiac efficiency. Shifting cardiac metabolism from free fatty acids (FA) towards glucose is a promising approach for the treatment of patients with stable angina, independently of the underling disease (macrovascular and/or microvascular disease). In this sense cardiac metabolic modulators open the way to a "revolutionary" understanding of ischemic heart disease and its common clinical manifestations, where myocardial ischemia is no longer considered as the mere oxygen and metabolites demand/supply unbalance, but as an energetic disorder. Keeping in mind such an alternative approach to the disease, development of new pharmacological agents directed toward multiple metabolic targets is mandatory.


Assuntos
Angina Estável/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Miocárdio/metabolismo , Angina Estável/metabolismo , Animais , Fármacos Cardiovasculares/farmacologia , Humanos
13.
Cardiovasc Drugs Ther ; 30(4): 393-398, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27417323

RESUMO

Percutaneous coronary intervention and anti-anginal medications have similar prognostic effectiveness in patients with chronic stable angina. The choice of optimal medical therapy for the management of chronic angina is of pivotal importance in patients with stable ischemic heart disease. The most commonly used anti-anginal agents have demonstrated equivalent efficacy in improving patient reported ischemic symptoms and quantitative exercise parameters. With regards to mortality, beta-blockers are beneficial only in the setting of depressed left ventricular systolic function after a recent myocardial infarction. Recent evidence suggests the lack of any benefit of beta-blockers in patients with preserved systolic function, even in the setting of prior myocardial infarction.Ranolazine is a non-haemodynamic anti-anginal agent. It is effective as adjunctive therapy in patients with chronic stable angina whose symptoms are un-adequately controlled by conventional treatment. The clinical development program of ranolazine has shown that the drug improves exercise performance, decreases angina and use of sublingual nitrates, compared to placebo. Ranolazine is well tolerated with neutral effect on haemodynamics. Besides its role in chronic stable angina, ranolazine has the potential for development in a number of other cardiovascular and non-cardiovascular conditions in the future.


Assuntos
Angina Estável/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Ranolazina/uso terapêutico , Angina Estável/metabolismo , Angina Estável/fisiopatologia , Animais , Fármacos Cardiovasculares/farmacocinética , Fármacos Cardiovasculares/farmacologia , Humanos , Ranolazina/farmacocinética , Ranolazina/farmacologia
14.
Mol Cell Proteomics ; 15(8): 2628-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27234505

RESUMO

Myocardial infarction (MI) triggers a potent inflammatory response via the release of circulatory mediators, including extracellular vesicles (EVs) by damaged cardiac cells, necessary for myocardial healing. Timely repression of inflammatory response are critical to prevent and minimize cardiac tissue injuries, nonetheless, progression in this aspect remains challenging. The ability of EVs to trigger a functional response upon delivery of carried bioactive cargos, have made them clinically attractive diagnostic biomarkers and vectors for therapeutic interventions. Using label-free quantitative proteomics approach, we compared the protein cargo of plasma EVs between patients with MI and from patients with stable angina (NMI). We report, for the first time, the proteomics profiling on 252 EV proteins that were modulated with >1.2-fold after MI. We identified six up-regulated biomarkers with potential for clinical applications; these reflected post-infarct pathways of complement activation (Complement C1q subcomponent subunit A (C1QA), 3.23-fold change, p = 0.012; Complement C5 (C5), 1.27-fold change, p = 0.087), lipoprotein metabolism (Apoliporotein D (APOD), 1.86-fold change, p = 0.033; Apolipoprotein C-III (APOCC3), 2.63-fold change, p = 0.029) and platelet activation (Platelet glycoprotein Ib alpha chain (GP1BA), 9.18-fold change, p < 0.0001; Platelet basic protein (PPBP), 4.72-fold change, p = 0.027). The data have been deposited to the ProteomeXchange with identifier PXD002950. This novel biomarker panel was validated in 43 patients using antibody-based assays (C1QA (p = 0.005); C5 (p = 0.0047), APOD (p = 0.0267); APOC3 (p = 0.0064); GP1BA (p = 0.0031); PPBP (p = 0.0465)). We further present that EV-derived fibrinogen components were paradoxically down-regulated in MI, suggesting that a compensatory mechanism may suppress post-infarct coagulation pathways, indicating potential for therapeutic targeting of this mechanism in MI. Taken together, these data demonstrated that plasma EVs contain novel diagnostic biomarkers and therapeutic targets that can be further developed for clinical use to benefit patients with coronary artery diseases (CADs).


Assuntos
Angina Estável/metabolismo , Biomarcadores/sangue , Vesículas Extracelulares/metabolismo , Infarto do Miocárdio/metabolismo , Proteômica/métodos , Idoso , Cromatografia Líquida , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Regulação para Cima
15.
Am J Cardiovasc Drugs ; 16(3): 221-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27021556

RESUMO

BACKGROUND: While recent guidelines have suggested the potential for beta-blockers as first-line agents in chronic stable angina, few data regarding comparative anti-anginal and metabolic effects between beta-blockers with and without vasodilating properties have been reported, particularly in patients with angina pectoris. OBJECTIVE: Our objective was to compare the anti-anginal and metabolic effects of carvedilol and atenolol in patients with stable angina pectoris. METHODS: A total of 89 patients (mean age 54.9 ± 9.3 years; male 53.9 %) with stable angina pectoris were randomly assigned to carvedilol (n = 43) or atenolol (n = 46). The subjects undertook an exercise treadmill test and completed the Seattle Angina Questionnaire (SAQ); metabolic parameters were measured at baseline and 6 months after treatment. RESULTS: The baseline characteristics of both groups were well balanced. Both carvedilol and atenolol significantly reduced heart rate from baseline (76 ± 11 to 66 ± 9 beat/min, p < 0.001; 74 ± 9 to 64 ± 9 beat/min, p < 0.001, respectively) with no significant changes in systolic and diastolic blood pressure. Improvement of time to ST-segment depression during the treadmill exercise and the SAQ scores for angina stability and frequency after 6 months of treatment were similar between groups. There was no significant change from baseline in the level of fasting glucose, insulin, or glycated hemoglobin in either group. However, total cholesterol and low-density lipoprotein cholesterol levels significantly reduced to a greater extent with carvedilol than with atenolol (-23 vs. -10 and -38 vs. -24 %, respectively, p < 0.05 for both), although the rate of statin use was comparable. No changes were seen in high-density lipoprotein cholesterol and triglyceride levels after 6 months of treatment in both groups compared with baseline. CONCLUSIONS: Both carvedilol and atenolol had a similar anti-anginal effect. Compared with atenolol, carvedilol might have more beneficial effects on lipid metabolism in patients with stable angina pectoris [ClinicalTrials.gov identifier: NCT02547597].


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Angina Estável/tratamento farmacológico , Atenolol/uso terapêutico , Carbazóis/uso terapêutico , Cardiotônicos/uso terapêutico , Coração/efeitos dos fármacos , Propanolaminas/uso terapêutico , Vasodilatadores/uso terapêutico , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Idoso , Angina Estável/complicações , Angina Estável/metabolismo , Angina Estável/fisiopatologia , Atenolol/efeitos adversos , Carbazóis/efeitos adversos , Cardiotônicos/efeitos adversos , Carvedilol , Colesterol/sangue , Teste de Esforço , Feminino , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Propanolaminas/efeitos adversos , República da Coreia/epidemiologia , Risco , Autorrelato , Vasodilatadores/efeitos adversos
16.
PLoS One ; 11(3): e0152029, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27003294

RESUMO

BACKGROUND: Asymmetric dimethylarginine (ADMA) is associated with increased risk of atherosclerotic cardiovascular disease and mortality through inhibition of nitrogen oxide (NO) synthesis. As positive correlations between serum concentrations of NO and body mass index (BMI) have been observed, we aimed to explore whether the potential associations between plasma ADMA levels and the risk of acute myocardial infarction (AMI) and mortality were modified by BMI. METHODS: Multivariable Cox proportional hazard models were used to estimate the hazard ratios (HR) for AMI, cardiovascular death and all-cause mortality according to baseline plasma ADMA levels in 4122 patients with suspected stable angina pectoris. Analyses were subsequently repeated in patients with BMI below (low BMI) or above (high BMI) median. RESULTS: A total of 2982 patients (72%) were men. Median (range) age, plasma ADMA level and BMI were 62 (21-88) years, 0.54 (0.10-1.25) µmol/L and 26.3 (18.5-54.3) kg/m2, respectively. During a mean (standard deviation) follow-up time of 4.7 (1.4) years, 337 (8%) patients suffered from an AMI, 300 (7%) died, whereof 165 (55%) due to cardiovascular disease. Each 0.1 µmol/L increment in plasma ADMA level was associated with an increased risk of AMI (HR (95% CI) 1.21 (1.08, 1.35) and cardiovascular death 1.30 (1.13, 1.49) in participants with low BMI only. Interactions were significant for AMI (p = 0.04) and CV death (p = 0.03). BMI did not modify the association between plasma ADMA levels and all-cause mortality. CONCLUSION: Plasma ADMA levels were associated with risk of AMI and cardiovascular death among patients with low BMI only.


Assuntos
Angina Estável/sangue , Arginina/análogos & derivados , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Angina Estável/metabolismo , Angina Estável/fisiopatologia , Arginina/sangue , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Óxidos de Nitrogênio/metabolismo , Noruega , Fatores de Risco
17.
Scand Cardiovasc J ; 50(4): 213-7, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26891417

RESUMO

Objective The aim of this study was to investigate the role of thiol disulfide homeostasis in the presence of slow coronary flow. Material and methods In this cross-sectional study, a total of 110 patients who admitted to our hospital between March 2014 and December 2015 were included in the study. There were 65 patients in the slow coronary flow, and 45 patients in the normal flow groups. Results We found significant differences between slow coronary flow and the normal flow groups for thiol disulfide homeostasis, and the results of our study indicated that hsCRP, and thiol disulfide ratio were independently associated with slow coronary flow. Conclusion Our study showed that thiol disulfide homeostasis was significantly and independently related to the presence of slow coronary flow.


Assuntos
Angina Estável , Angiografia Coronária/métodos , Vasos Coronários , Estresse Oxidativo/fisiologia , Compostos de Sulfidrila/metabolismo , Adulto , Idoso , Angina Estável/diagnóstico , Angina Estável/metabolismo , Circulação Coronária , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/metabolismo , Vasos Coronários/fisiopatologia , Dissulfetos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatística como Assunto
18.
Coron Artery Dis ; 27(2): 104-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26580301

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a common complex disease caused by atherosclerosis. Autophagy is a cellular degradation process that delivers long-lived macromolecules and dysfunctional organelles into lysosomes for digestion. Autophagy regulates lipid and cholesterol metabolism. We have previously shown that expression of autophagic and lysosomal genes is altered in CAD patients. In this study, we investigated gene expression of a lysosomal hydrolase, acid α-glucosidase (GAA), in CAD patients and controls. METHODS: GAA gene expression was examined in large cohorts of CAD patients (n=248) and ethnically matched controls (n=208). GAA enzymatic activity, protein levels, and transcript levels were determined and compared between CAD patients and controls. RESULTS: GAA activities in CAD patients were significantly elevated (P<0.05) compared with controls. Consistently, GAA transcription levels were also significantly increased in CAD patients (P<0.01). Multivariate logistic regression analyses (GAA transcript level, hypertension, diabetes, and smoking) revealed that GAA transcript levels were strongly associated with CAD (odds ratio 5.93, 95% confidence interval 2.98-11.78, P=3.89×10(-7)). GAA protein levels were insignificantly increased in CAD patients (P>0.05), likely due to assay insensitivity. CONCLUSION: Compared with controls, GAA gene expression levels in CAD patients were significantly increased, suggesting that GAA may be involved in the CAD development.


Assuntos
Doença da Artéria Coronariana/genética , Isquemia Miocárdica/genética , RNA Mensageiro/metabolismo , alfa-Glucosidases/genética , Idoso , Angina Estável/genética , Angina Estável/metabolismo , Angina Instável/genética , Angina Instável/metabolismo , Western Blotting , Estudos de Casos e Controles , Estudos de Coortes , Doença da Artéria Coronariana/metabolismo , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Razão de Chances , Reação em Cadeia da Polimerase Via Transcriptase Reversa , alfa-Glucosidases/metabolismo
19.
Kardiologiia ; 56(3): 5-11, 2016 Mar.
Artigo em Russo | MEDLINE | ID: mdl-28294882

RESUMO

Great number of factors stimulating or inhibiting production of proteins in inflammatory process influence serum levels of markers of inflammation. A number of homozygous genotypes of inflammation, destruction, and angiogenesis genes have been found to be associated with basic clinical-laboratory indices of inflammation and atherosclerotic process. The revealed genetic markers can be used as complimentary markers of prognosis of the disease course.


Assuntos
Angina Estável/genética , Angina Estável/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Biomarcadores , Homozigoto , Humanos , Inflamação/genética , Masculino , Prognóstico
20.
PLoS One ; 10(10): e0140958, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26485305

RESUMO

Small non-coding microRNAs (miRNAs) are implicated in gene regulation, including those involved in coronary artery disease (CAD). Our aim was to identify whether specific serum miRNAs present in the circulating lipoproteins (Lp) are associated with stable or vulnerable CAD patients. A cardiovascular disease-focused screening array was used to assess miRNAs distribution in sera collected from 95 CAD patients: 30 with stable angina (SA), 39 with unstable angina (UA), 26 at one month after myocardial infarction (MI) and 16 healthy control subjects. We found that miR-486, miR-92a and miR-122 presented the highest expression in CAD sera. These miRNA together with miR-125a, miR-146a and miR-33a were further individually analyzed by TaqMan assays. The results were consistent with PCR-array screening data that all of these miRNAs were significantly increased in CAD patients compared to controls. Using a binary logistic regression model, we established that miR-486 and miR-92a in association with some high-density lipoprotein (HDL) components can designate vulnerable CAD patients. Further, all classes of Lp were isolated from sera by density gradient ultracentrifugation. Analysis of the selected miRNAs in each Lp class showed that they were associated mainly with HDL, miR-486 and miR-92a having the highest levels. In UA and MI patients, miR-486 prevailed in HDL2, while miR-92a prevailed in HDL3, and their levels discriminate between stable and vulnerable CAD patients. We identified two circulating miRNAs that in association with some lipid metabolism biomarkers can be used as an additional tool to designate vulnerable CAD patients.


Assuntos
Angina Estável/diagnóstico , Angina Instável/diagnóstico , Doença da Artéria Coronariana/diagnóstico , Lipoproteínas HDL/sangue , MicroRNAs/metabolismo , Infarto do Miocárdio/diagnóstico , Adulto , Idoso , Angina Estável/metabolismo , Angina Instável/metabolismo , Biomarcadores/metabolismo , Doença da Artéria Coronariana/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Infarto do Miocárdio/metabolismo , Adulto Jovem
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