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1.
Life Sci ; 270: 119065, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33460661

RESUMO

AIMS: Coronary heart disease (CHD), a chronic inflammatory condition of vascular endothelial cells (VECs), poses a serious threat to human health. Previous studies have found that microRNAs (miRNAs) are closely related to the occurrence and development of cardiac diseases. Therefore, this study focused on the regulation by miR-323-3p on the progression of CHD. METHODS: Initially, we employed microarray-based gene expression profiling of CHD to identify differentially expressed miRNAs. Next, the expression of miR-323-3p and SIRT1 was detected by RT-qPCR in a rat model of CHD generated by feeding with a high-fat diet. The interaction between miR-323-3p and SIRT1 was identified using bioinformatics analysis and dual luciferase reporter gene assay. The expressions of miR-323-3p and SIRT1 were altered in CHD rats and vascular endothelial cells (VECs) to examine the specific effects on CHD. RESULTS: miR-323-3p was observed to be highly-expressed in blood samples from patients with CHD or with mild atherosclerosis and in the rat model of CHD. SIRT1 was a target gene of miR-323-3p, which could downregulate SIRT1 expression. miR-323-3p overexpression or SIRT1 inhibition resulted in increased apoptosis of VECs, elevated ac-p65 protein expression and ratio of ac-p65/p65, and upregulated expression of NF-κB signaling pathway-related proteins. Besides, miR-323-3p inhibition or SIRT1 upregulation in the CHD rat model was found to significantly alleviate symptoms and decrease levels of proteins related to the ac-p65 and NF-κB signaling pathways. CONCLUSION: Overall, the experimental data provide evidence that miR-323-3p suppression may restrain VEC apoptosis and prevent the resultant CHD progression via SIRT1-inactivatedNF-κB signaling pathway.


Assuntos
Doença das Coronárias/genética , MicroRNAs/genética , Sirtuína 1/metabolismo , Adulto , Animais , Apoptose/genética , Linhagem Celular , Proliferação de Células/genética , China , Doença das Coronárias/metabolismo , Células Endoteliais/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Ratos , Transdução de Sinais/fisiologia , Sirtuína 1/genética
2.
Biomed Pharmacother ; 134: 111165, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33370633

RESUMO

High platelet reactivity and gastric mucosal injury after aspirin (ASA) treatment are associated with poor compliance and an increased risk of cardiovascular events. Panax notoginseng saponins (PNS) have been widely used for the treatment of coronary heart disease (CHD) in addition to antiplatelet drugs in China; however, the joint effect and possible mechanism of PNS in addition to ASA on platelet activation and gastric injury remain unclear. This study was designed to investigate the combinational effects of PNS with ASA, and to explore the underlying mechanism via arachidonic acid (AA) metabolism pathway using lipidomic analysis. In a randomized, assessor-blinded trial, 42 patients with stable coronary heart disease (SCHD) and chronic gastritis were randomly assigned to receive ASA (n = 21) or PNS + ASA (n = 21) for 2 months. Compared with ASA alone, PNS + ASA further inhibited CD62p expression, GPIIb-IIIa activation and platelet aggregation and led to increased platelet inhibition rate. PNS + ASA suppressed the activity of platelet cyclooxygenase (COX)-1, and decreased the production of TXB2, PGD2, PGE2, 11-HETE, the downstream oxylipids of AA/COX-1 pathway in platelets, compared with ASA alone. The severity of dyspepsia assessment (SODA) results showed that patients in PNS + ASA group exhibited relieved dyspeptic symptoms as compared with those in ASA group, which might be associated with enhanced secretion of gastrin and motilin. In vivo study of myocardial infarction rats demonstrated that PNS attenuated ASA-induced gastric mucosal injury, which was related to markedly boosted gastric level of 6,15-diketo-13,14-dihydro-prostaglandin (PG)F1α, 13,14-dihydro-15-keto-PGE2 and PGE2 from AA/PG pathway in response to PNS + ASA compared with ASA alone. In summary, our study demonstrated that the combination of PNS and ASA potentiated the antiplatelet effect of ASA via AA/COX-1/TXB2 pathway in platelets, and mitigated ASA-related gastric injury via AA/PG pathway in gastric mucosa.


Assuntos
Ácido Araquidônico/metabolismo , Aspirina/uso terapêutico , Plaquetas/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Mucosa Gástrica/efeitos dos fármacos , Gastrite/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Panax notoginseng , Extratos Vegetais/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Saponinas/uso terapêutico , Adulto , Idoso , Animais , Aspirina/efeitos adversos , Pequim , Plaquetas/metabolismo , Doença Crônica , Doença das Coronárias/diagnóstico , Doença das Coronárias/metabolismo , Citoproteção , Sinergismo Farmacológico , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/diagnóstico , Gastrite/metabolismo , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/isolamento & purificação , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Panax notoginseng/química , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Inibidores da Agregação de Plaquetas/efeitos adversos , Ratos Wistar , Saponinas/efeitos adversos , Saponinas/isolamento & purificação , Fatores de Tempo , Resultado do Tratamento
3.
Am J Clin Nutr ; 112(2): 268-283, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32520313

RESUMO

BACKGROUND: The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer. OBJECTIVE: The aim was to assess the association of 2 derived dietary pattern scores with serum metabolites and identify metabolic pathways associated with the metabolites. METHODS: We evaluated the cross-sectional association between each dietary pattern (WD, PD) and metabolites in 2199 Women's Health Initiative (WHI) participants. With FFQ and factor analysis, we determined 2 dietary patterns consistent with WD and PD. Metabolites were measured with LC-tandem MS. Metabolite discovery among 904 WHI Observational Study (WHI-OS) participants was replicated among 1295 WHI Hormone Therapy Trial (WHI-HT) participants. We analyzed each of 495 metabolites with each dietary score (WD, PD) in linear regression models. RESULTS: The PD included higher vegetables and fruit intake compared with the WD with higher saturated fat and meat intake. Independent of energy intake, BMI, physical activity, and other confounding variables, 45 overlapping metabolites were identified (WHI-OS) and replicated (WHI-HT) with an opposite direction of associations for the WD compared with the PD [false discovery rate (FDR) P < 0.05]. In metabolite set enrichment analyses, phosphatidylethanolamine (PE) plasmalogens were positively enriched for association with WD [normalized enrichment score (NES) = 2.01, P = 0.001, FDR P = 0.005], and cholesteryl esters (NES = -1.77, P = 0.005, FDR P = 0.02), and phosphatidylcholines (NES = -1.72, P = 0.01, P = 0.03) were negatively enriched for WD. PE plasmalogens were positively correlated with saturated fat and red meat. Phosphatidylcholines and cholesteryl esters were positively correlated with fatty fish. CONCLUSIONS: Distinct metabolite signatures associated with Western and Prudent dietary patterns highlight the positive association of mitochondrial oxidative stress and lipid dysregulation with a WD and the inverse association with a PD.


Assuntos
Doença das Coronárias/metabolismo , Dieta Saudável , Dieta Ocidental/efeitos adversos , Neoplasias/metabolismo , Idoso , Estudos Transversais , Gorduras/metabolismo , Comportamento Alimentar , Feminino , Humanos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Estresse Oxidativo , Verduras/metabolismo
4.
Am J Physiol Heart Circ Physiol ; 318(5): H1256-H1271, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32223553

RESUMO

Despite decades of research on the pathophysiology of myocardial stunning, protein changes and/or phosphorylation status underlying alterations in cardiac function/structure remain inadequately understood. Here, we utilized comprehensive and quantitative proteomic and phosphoproteomic approaches to explore molecular mechanisms of myocardial stunning in swine. The closed-chest swine (n = 5 pigs) were subjected to a 10-min left anterior descending coronary artery (LAD) occlusion producing regional myocardial stunning. Tissues from the ischemic LAD region and a remote nonischemic area of the left ventricle were collected 1 h after reperfusion. Ion current-based proteomics (IonStar) and quantitative phosphoproteomics were employed in parallel to identify alterations in protein level and site-specific phosphorylation changes. A novel swine heart protein database exhibiting high accuracy and low redundancy was developed here to facilitate comprehensive study. Further informatic investigations identified potential protein-protein interactions in stunned myocardium. In total, we quantified 2,099 protein groups and 4,699 phosphorylation sites with only 0.4% missing values. Proteomic analyses revealed downregulation of contractile function and extracellular matrix remodeling. Meanwhile, alterations in phosphorylation linked with contractile dysfunction and apoptotic cell death were uncovered. NetworKIN/STRING analysis predicted regulatory kinases responsible for altered phosphosites, such as protein kinase C-mediated phosphorylation of cardiac troponin I-S199 and CaMKII-mediated phosphorylation of phospholamban-T17. In summary, the ion current-based proteomics and phosphoproteomics reliably identified novel alterations in protein content and phosphorylation contributing to contractile dysfunction, extracellular matrix (ECM) damage, and programmed cell death in stunned myocardium, which corroborate well with our physiological observations. Moreover, this work developed a comprehensive database of the swine heart proteome, a highly valuable resource for future translational research in porcine models with cardiovascular diseases.NEW & NOTEWORTHY We first used ion current-based proteomics and phosphoproteomics to reliably identify novel alterations in protein expression and phosphorylation contributing to contractile dysfunction, extracellular matrix (ECM) damage, and programmed cell death in stunned myocardium and developed a comprehensive swine heart-specific proteome database, which provides a valuable resource for future research in porcine models of cardiovascular diseases.


Assuntos
Doença das Coronárias/metabolismo , Miocárdio/metabolismo , Fosfoproteínas/metabolismo , Proteoma/metabolismo , Potenciais de Ação , Animais , Doença das Coronárias/genética , Doença das Coronárias/fisiopatologia , Masculino , Contração Miocárdica , Fosfoproteínas/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteoma/genética , Suínos
5.
Metabolism ; 107: 154231, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32298723

RESUMO

BACKGROUND: The mechanism of pyruvate kinase M2 (PKM2)-mediated inflammatory signalling in macrophages when plaques rupture and the impact of hyperglycaemia on the signalling are unclear. The present study aimed to explore the impact of hyperglycaemia on PKM2-mediated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome/stress granule signalling in macrophages and its correlation with plaque vulnerability in vivo and in vitro. METHODS: From July to December 2019, 80 patients with coronary heart disease (CHD) were divided into acute ST-segment elevation myocardial infarction (STEMI) (n = 57) (DM-STEMI, n = 21; non-DM-STEMI, n = 36) and stable CHD (SCHD) groups (n = 23). Circulating mononuclear cells were isolated. The value of peak troponin I (TnI), the Global Registry of Acute Coronary Events (GRACE) risk score, and the expression levels of the related markers were quantified and compared. In vitro studies on the THP-1 cells were also performed. RESULTS: The DM-STEMI group had a higher value of peak TnI and a higher GRACE risk score than the non-DM-STEMI group (p < 0.05). The highest expression levels of PKM2, NLRP3, interleukin (IL)-1ß, and IL-18 and the lowest expression level of GTPase activating protein (SH3 domain)-binding protein 1 (G3BP1) (a stress granule marker protein) were observed in the DM-STEMI group, and they were followed by the non-DM-STEMI group and the SCHD group (p < 0.05). In vitro studies showed similar results and that TEPP-46 (a PKM2 activator) and 2-deoxy-d-glucose (a toxic glucose analogue) reversed the hyperglycaemia-induced increase in the NLRP3 inflammasome and decrease in G3BP1 expression. CONCLUSION: Hyperglycaemia might increase the activation of PKM2-mediated NLRP3 inflammasome/stress granule signalling and increase plaque vulnerability, associating it with worse prognosis. PKM2 may be a novel prognostic indicator and a new target for the treatment of patients with CHD and DM.


Assuntos
Proteínas de Transporte/metabolismo , Grânulos Citoplasmáticos , Hiperglicemia/fisiopatologia , Inflamassomos , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Placa Aterosclerótica/metabolismo , Hormônios Tireóideos/metabolismo , Idoso , Linhagem Celular , Doença das Coronárias/metabolismo , DNA Helicases/sangue , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a Poli-ADP-Ribose/sangue , RNA Helicases/sangue , Proteínas com Motivo de Reconhecimento de RNA/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Troponina I/metabolismo
6.
Exp Mol Pathol ; 114: 104412, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32113905

RESUMO

Coronary heart disease (CHD) is the major cause of death in modern society. CHD is characterized by atherosclerosis, which could lead to vascular cavity stenosis or obstruction, resulting in ischemic cardiac conditions such as angina and myocardial infarction. In terms of the mitochondrion, the main function is to produce adenosine triphosphate (ATP) for cells. And the alterations (including mutations, altered copy number and haplogroups) of mitochondrial DNA (mtDNA) are associated with the abnormal expression of oxidative phosphorylation (OXPHOS) system, resulting in mitochondrial dysfunction, then leading to perturbation on the electron transport chain and increased ROS generation and reduction in ATP level, contributing to ATP-producing disorders and oxidative stress, which may further accelerate development or vulnerability of atherosclerosis and myocardial ischemic injury. Therefore, the mtDNA defects may play an important role in making an early diagnosis, identifying disease-specific biomarkers and therapeutic targets, and predicting outcomes for patients with atherosclerosis and CHD. In this review, we aim to summarize the contribution of mtDNA mutations, altered mtDNA copy number and mtDNA haplogroups on the occurrence and development of CHD.


Assuntos
Aterosclerose/genética , Doença das Coronárias/genética , DNA Mitocondrial/genética , Estresse Oxidativo/genética , Trifosfato de Adenosina/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Doença das Coronárias/metabolismo , Doença das Coronárias/patologia , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação/genética , Fosforilação Oxidativa , Espécies Reativas de Oxigênio/metabolismo
7.
Sci Rep ; 10(1): 5638, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221337

RESUMO

This study aimed to investigate the prognostic value of high-sensitivity creatine kinase-myocardial band or fraction (hsCK-MB) in comparison with other well-established biomarkers including heart type-fatty acid binding protein (H-FABP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable coronary heart disease (SCHD). A total of 1,785 patients were enrolled and followed for 36 months. The primary outcome was all-cause mortality. The secondary outcomes included cardiovascular (CV) death, acute myocardial infarction (AMI), angina-related hospitalizations, and hospitalizations for heart failure. The all-cause mortality rate was significantly higher in the high hsCK-MB group compared to the low hsCK-MB group (4.64% vs. 1.88%, p = 0.0026). After adjusting for baseline covariates, there were no significant differences for the secondary outcomes. H-FABP (≥4.226 ng/mL) was the best predictor for all-cause mortality (HR = 2.68, 95% CI = 1.28-5.62, p = 0.009) and CV death (HR = 6.84, 95% CI = 1.89-22.14, p = 0.003). The high NT-proBNP group had a higher AMI-related hospitalization rate (HR = 1.91, 95% CI = 1.00-3.65, p = 0.05). Neither the addition of hsCK-MB to any other markers nor combinations of the three markers improved the prognostic significance of CV outcomes. In conclusion, hsCK-MB was an independent predictor for all-cause mortality but not CV outcomes in patients with SCHD. Combination of hsCK-MB, H-FABP and NT-proBNP failed to improve the prognostic power for all-cause mortality or CV outcomes.


Assuntos
Doença das Coronárias/metabolismo , Creatina Quinase Forma MB/metabolismo , Adulto , Biomarcadores/metabolismo , Doença das Coronárias/mortalidade , Proteínas de Ligação a Ácido Graxo/metabolismo , Feminino , Seguimentos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/mortalidade , Prognóstico
8.
Sci Rep ; 10(1): 1652, 2020 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015361

RESUMO

Endothelin 1 (ET-1) has been shown to have a key role in homeostasis and function of endothelium and maybe fundamental in the relationship between coronary heart disease (CHD) and periodontitis. In this trial, we assessed the influence on serum and salivary ET-1 levels of gingival health, CHD, periodontitis, or a combination of periodontitis-CHD. Clinical and periodontal parameters, were collected from periodontitis patients (n = 34), CHD patients (n = 34), periodontitis + CHD patients (n = 34), and from healthy patients (n = 34) together with saliva and serum samples. The median concentrations of salivary and serum ET-1 were significantly higher in the CHD patients [serum: 1.4(1.1-1.6) pg/ml; saliva 1.2 (0.9-1.6) µmol/g, p < 0.01] and in the periodontitis + CHD patients [serum: 1.7 (1.2-21.8) pg/ml; salivary 1.4(1-1.6) µmol/g, p < 0.001] respect to periodontitis and control patients. Through a univariate regression analysis, c-reactive protein (CRP) and CHD (both p < 0.001) and periodontitis (p = 0.029) were statistically correlated with ET-1 in serum. The multivariate regression analysis demonstrated that only CRP was the statistically predictor of ET-1 in serum(p < 0.001). The multivariate regression analysis in saliva demonstrated that, regarding ET-1 levels the only predictor were CRP (p < 0.001) and total cholesterol (p = 0.042). The present study evidenced that subjects with CHD and periodontitis plus CHD had higher serum and salivary levels of ET-1 compared to subjects with periodontitis and healthy controls. Moreover, only CRP remained a major predictor of increased ET-1 concentrations in both serum and saliva.


Assuntos
Endotelina-1/sangue , Endotelina-1/metabolismo , Periodontite/sangue , Periodontite/metabolismo , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Doença das Coronárias/sangue , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Feminino , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Periodontite/complicações , Saliva/metabolismo
9.
Am J Cardiol ; 125(8): 1194-1201, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32106929

RESUMO

The role of NT-proBNP and hs-cTnT levels in predicting heart failure (HF) and cardiovascular disease (CVD) events in persons with prediabetes (pre-DM) and diabetes mellitus (DM) is not well-established. We examined the individual and combined relations of N-terminal natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels among asymptomatic adults with pre-DM and DM with the development of incident HF and CVD events. 5,584 participants with biomarker measures aged 45 to 84 years were included from the Multi-Ethnic Study of Atherosclerosis, of which 4,090 were normoglycemic, 799 had pre-DM, and 695 had DM at baseline and were followed for 12.4 ± 3.8 years. In those with DM, HF incidence rates per 1,000 person-years ranged from 3.2 to 39.4 across quartiles of NT-proBNP and 0.6 to 18.2 for hs-cTnT, respectively. Corresponding values for CVD incidence per 1,000 person-years ranged from 13.7 to 39.4 for NT-proBNP and 13.2 to 35.4 for hs-cTnT. Multivariate adjusted HRs were highest when both NT-proBNP and hs-cTnT were above versus below the median in those with pre-DM/DM (16.7 for incident HF and 2.1 for CVD events, both p <0.01). In conclusion, the combination of both biomarkers to traditional risk factors in participants who were normoglycemic or with pre-DM or DM improved risk prediction for both incident HF and total CVD events in an ethnically diverse population.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Insuficiência Cardíaca/metabolismo , Isquemia Miocárdica/metabolismo , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Estado Pré-Diabético/metabolismo , Acidente Vascular Cerebral/metabolismo , Troponina T/metabolismo , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/epidemiologia , Angina Pectoris/metabolismo , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doença das Coronárias/metabolismo , Doença das Coronárias/mortalidade , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/mortalidade , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Estados Unidos/epidemiologia
10.
J Agric Food Chem ; 68(5): 1266-1275, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31937103

RESUMO

Diabetes (T2DM) is a major global health issue, and developing new approaches to its prevention is of paramount importance. We hypothesized that abnormalities in lipid metabolism are involved in alpha-cell deregulation. We therefore studied the metabolic factors underlying alpha-cell dysfunction in T2DM progression after a dietary intervention (Mediterranean and low-fat). Additionally, we evaluated whether postprandial glucagon levels may be considered as a predictive factor of T2DM in cardiovascular patients. Non-T2DM participants from the CORDIOPREV study were categorized by tertiles of the area under the curve (AUC) for triacylglycerols and also by tertiles of AUC for glucagon. Our results showed that patients with higher triacylglycerols levels presented elevated postprandial glucagon (P = 0.009). Moreover, we observed higher risk of T2DM (hazard ratio: 2.65; 95% confidence interval: 1.56-4.53) in subjects with elevated glucagon. In conclusion, high postprandial lipemia may induce alpha-cell dysfunction in cardiovascular patients. Our results also showed that postprandial glucagon levels could be used to predict T2DM development.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Células Secretoras de Glucagon/metabolismo , Hiperlipidemias/metabolismo , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Progressão da Doença , Feminino , Glucagon/metabolismo , Humanos , Hiperlipidemias/complicações , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Estudos Prospectivos , Triglicerídeos/metabolismo
11.
J Atheroscler Thromb ; 27(2): 105-118, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31748469

RESUMO

Animal models that closely resemble both human disease findings and their onset mechanism have contributed to the advancement of biomedical science. The Watanabe heritable hyperlipidemic (WHHL) rabbit and its advanced strains (the coronary atherosclerosis-prone and the myocardial infarction-prone WHHL rabbits) developed at Kobe University (Kobe, Japan), an animal model of human familial hypercholesterolemia, have greatly contributed to the elucidation of the pathophysiology of human lipoprotein metabolism, hypercholesterolemia, atherosclerosis, and coronary heart disease, as described below. 1) The main part of human lipoprotein metabolism has been elucidated, and the low-density lipoprotein (LDL) receptor pathway hypothesis derived from studies using fibroblasts was proven in vivo. 2) Oxidized LDL accumulates in the arterial wall, monocyte adhesion molecules are expressed on arterial endothelial cells, and monocyte-derived macrophages infiltrate the arterial intima, resulting in the formation and progression of atherosclerosis. 3) Coronary lesions differ from aortic lesions in lesion composition. 4) Factors involved in the development of atherosclerosis differ between the coronary arteries and aorta. 5) The rupture of coronary lesions requires secondary mechanical forces, such as spasm, in addition to vulnerable plaques. 6) Specific lipid molecules in the blood have been identified as markers of the progression of coronary lesions. At the end of the breeding of the WHHL rabbit family at Kobe University, this review summarizes the history of the development of the WHHL rabbit family and their contribution to biomedical science.


Assuntos
Aterosclerose , Doença das Coronárias , Modelos Animais de Doenças , Hiperlipoproteinemia Tipo II , Coelhos , Animais , Aterosclerose/história , Aterosclerose/metabolismo , Aterosclerose/prevenção & controle , Doença das Coronárias/história , Doença das Coronárias/metabolismo , Doença das Coronárias/prevenção & controle , História do Século XX , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/história , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/história , Hiperlipoproteinemia Tipo II/metabolismo , Metabolismo dos Lipídeos/fisiologia
12.
Biomed Pharmacother ; 121: 109655, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734577

RESUMO

Coronary heart disease (CHD) is a leading cause of death and disability worldwide. Huoxue Anxin Recipe (HAR) is a novel Chinese Herbal Medicine formula of that has been used to treat CHD for several decades. Our previous study found that HAR had anti-oxidative effects, and could promote myocardial angiogenesis and improve cardiac function following myocardial infarction (MI) in rats. However, the active compounds, potential targets, and biological processes related to HAR have not been systematically investigated. Here, network pharmacology and experimental validation were used to study the protective mechanisms of HAR against CHD. We identified 124 active components, 124 verified targets, and 111 predictive targets. A total of 1192 genes related to CHD were identified by cDNA microarray and database analysis. A total of 47 putative targets of HAR against CHD were identified, including 32 verified targets and 15 predictive targets. ClueGo enrichment analysis identified 49 biological processes involved in the anti-CHD effects of HAR. Among them, the negative regulation of blood coagulation and regulation of collagen biosynthetic process were experimentally validated. After constructing a protein-protein interaction network and clustering with MECODE and ClusterONE, 162 key proteins (from ClueGo and clustering) were used to construct an internal interaction network. Complement C3 (C3), Fibrinogen alpha (FGA), Fibrinogen gamma (FGG), interleukin-6 (IL6), and Apolipoprotein A1 (APOA1) were the top 5 hub proteins identified by cytoHubber analysis. HAR limited the concentrations of C3, FGA, FGG, and IL6 and increased APOA1 levels. The results indicated that HAR could down-regulate blood coagulation, regulate collagen biosynthesis, inhibit peroxidation and inflammation injury, and promote cholesterol efflux. HAR could be a potential source of novel and effective drugs for CHD.


Assuntos
Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Animais , Apolipoproteína A-I/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Colágeno/metabolismo , Complemento C3/metabolismo , Doença das Coronárias/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fibrinogênio/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-16/metabolismo , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Sci Rep ; 9(1): 19273, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848411

RESUMO

According to guidelines, individuals with familial hypercholesterolemia (FH) shall receive lifestyle intervention and intensive lipid-lowering treatment from early in life to reduce the risk of coronary heart disease. Our aim was to study if treatment of FH also could affect risk of lifestyle-related cancer. We presented cumulative incidence of total cancer and lifestyle-related cancer sites in individuals with genetically verified FH (n = 5531) compared with age and sex matched controls (n = 108354). Individuals with FH had 20% lower risk of smoking-related cancer compared with the control population [HR 0.80 (95% CI, 0.65-0.98)], in particular men with FH at 40-69 years at age of diagnosis with HR 0.69 (95% CI, 0.49-0.97). The FH population and controls had similar rates of total cancer [HR 0.97 (95% CI, 0.86-1.09)], cancer related to poor diet [HR 0.82 (95% CI, 0.59-1.15)], cancer related to physical inactivity [HR 0.93 (95% CI, 0.73-1.18)], alcohol-related cancer [HR 0.98 (95% CI, 0.80-1.22)] and cancer related to obesity [HR 1.03 (95% CI, 0.89-1.21)]. In summary, we found reduced risk of smoking-related cancer in individuals with FH, most likely due to a lower prevalence of smoking. Implications of these findings can be increased motivation and thus compliance to treatment of hypercholesterolemia.


Assuntos
LDL-Colesterol/metabolismo , Hiperlipoproteinemia Tipo II/epidemiologia , Metabolismo dos Lipídeos , Neoplasias/epidemiologia , Adulto , Idoso , Estudos de Coortes , Doença das Coronárias/complicações , Doença das Coronárias/epidemiologia , Doença das Coronárias/metabolismo , Doença das Coronárias/patologia , Feminino , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/metabolismo , Hiperlipoproteinemia Tipo II/patologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Neoplasias/induzido quimicamente , Neoplasias/complicações , Neoplasias/metabolismo , Fatores de Risco , Fumar/efeitos adversos , Fumar Tabaco/efeitos adversos
15.
Food Funct ; 10(11): 7461-7475, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31667483

RESUMO

BACKGROUND AND PURPOSE: Molecular mechanisms of atherogenesis are considered to be emerging therapeutic targets for atherosclerosis prevention. Cell and animal studies have shown that crocetin can decelerate atherogenesis. However, the anti-atherogenic properties of crocetin in humans are still ambiguous. METHODS AND RESULTS: Fifty clinically diagnosed CAD patients were randomly divided into two parallel groups, crocetin and placebo, who received one capsule of crocetin (10 mg) and placebo per day, respectively, for two months. Serum circulating homocysteine (Hcy) [-1.09 (-1.64 to -0.54) µM, P = 0.001], heart-type fatty acid binding protein (h-FABP) [-2.07 (-2.72 to -1.43) ng mL-1, P = 0.001], intercellular adhesion molecule 1 [-14.92 (-21.92 to -7.92) ng mL-1, P = 0.001], vascular cell adhesion molecule 1 [-18.61 (-29.73 to -7.49) ng mL-1, P = 0.002], and monocyte chemoattractant protein 1 [-4.67 (-6.50 to -2.83) pg mL-1, P = 0.001] decreased significantly after the trial in the crocetin group, while high-density lipoprotein (HDL) significantly increased [+4.21 (0.68 to 7.73) mg mL-1, P = 0.021]. Also, systolic [-0.21 (-0.32 to -0.10) mmHg, P = 0.001] and diastolic [-0.20 (-0.34 to -0.07) mmHg, P = 0.004] blood pressures decreased significantly in the crocetin group. Nevertheless, clinically significant percentage changes were only observed in Hcy (-15.25 ± 3.15, µM), HDL (-10.70 ± 5.06, mg dL-1), and h-FABP (-21.10 ± 3.09, ng mL-1) in the crocetin group. Furthermore, the relative increase in the gene expressions of sirtuin1 and AMP-activated protein kinase and a decrease in the lectin-type oxidized LDL receptor 1 and nuclear factor-kappa B expression in isolated peripheral blood mononuclear cells in the crocetin group were significant at the end of the trial in comparison with the placebo. CONCLUSION: As the first human study, we showed the ability of crocetin to alter the expression of atherogenic genes and endothelial cell adhesion molecules in CAD patients. It appears that crocetin could be considered as a promising anti-atherogenic candidate for future studies.


Assuntos
Aterosclerose/tratamento farmacológico , Carotenoides/farmacologia , Doença das Coronárias/metabolismo , Biomarcadores/sangue , Carotenoides/administração & dosagem , Doença das Coronárias/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco
16.
Sci Rep ; 9(1): 17237, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754227

RESUMO

To assess the impact of sex on office white-coat effect tail (OWCET), the waning of systolic blood pressure (SBP) after its waxing during office visit, on the incidence of long-term major fatal and non-fatal events in two Italian residential cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. There were 3565 persons (92 with missing data, 44% men, 54 ± 11 years) included in the Gubbio and 1712 men (49 ± 5 years) in the IRA studies. OWCET was defined as a decrease of ≥10 mmHg in SBP between successive measurements with slight measurement differences between the two cohorts. Cardiovascular (CVD), coronary heart disease (CHD) and stroke (STR) incidences were considered. Over an approximately 20-year follow-up, women with OWCET had an increased risk of CVD [HR: 1.591 (95%CI: 1.204-2.103)], CHD [HR: 1.614 (95%CI: 1.037-2.512)] and STR [HR: 1.696 (95%CI: 1.123-2.563)] events independently of age, serum and HDL cholesterol, cigarettes, BMI and SBP in the Gubbio study. However, there was no increased risk of CVD, CHD or STR in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. These results were not modified significantly by the correction of the regression dilutions bias between the first and the subsequent SBP measurements. Thus, in primary care, OWCET should be actively evaluated in women as it can improve stratification of long-term CVD, CHD and STR risks.


Assuntos
Doença das Coronárias/etiologia , Acidente Vascular Cerebral/etiologia , Pressão Sanguínea/fisiologia , Causas de Morte , HDL-Colesterol/metabolismo , Estudos de Coortes , Doença das Coronárias/metabolismo , Feminino , Humanos , Incidência , Itália , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Fatores de Risco , Acidente Vascular Cerebral/metabolismo
18.
BMC Genomics ; 20(1): 862, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726978

RESUMO

BACKGROUND: Previous study reported that patients who suffered coronary heart disease (CHD) complicated with non-alcoholic fatty liver disease (NAFLD) had worse cardiac function and clinical outcomes than patients with CHD only. Notably, the mechanism is still unclear. This study aimed to investigate the changes and roles of intestinal bacterial microbiota in CHD-NAFLD patients. METHODS AND RESULTS: People were recruited and divided into three groups, including CHD patients (without NAFLD), CHD-NAFLD patients and healthy controls (HCs). Each group contained 24 people. Fecal samples and clinical information were carefully collected. The Illumina sequencing of 16S rRNA was applied to profile the overall structure of the fecal bacterial microbiota and the characteristics of the bacterial microbiota based on the Operational Taxonomic Units. In clinical information, the CHD-NAFLD patients showed an increase in BMI, uric acid and triglyceride. There was a significant reduction in the abundance of Parabacteroides and Collinsella in overall CHD patients (including CHD-NAFLD and CHD patients). The intestinal bacterial microbiota in CHD-NAFLD patients showed an increase in the abundance of Copococcus and Veillonella, and a reduction in the abundance of Parabacteroides, Bacteroides fragilis, Ruminococcus gnavus, Bacteroides dorei, and Bifidobacterium longum subsp infantis. Among them, the abundance of Ruminococcus gnavus and Bacteroides dorei was significantly lower than that in CHD patients. Additionally, BMI positively correlated with the abundance of Copococcus and negatively correlated with the abundance of Bifidobacterium longum subsp infantis. The abundance of Veillonella positively correlated with AST. The abundance of Bacteroides dorei negatively correlated with ALT and AST. It indicates that the abundance of intestinal microbiota was related to the changes in clinical indexes. CONCLUSIONS: Changes of intestinal bacterial microbiota in CHD-NAFLD patients may be important factors affecting the degree of metabolic disorder, which may be one of the important reasons for the worse clinical outcome and disease progression in CHD-NAFLD patients than in CHD patients.


Assuntos
Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Idoso , Bactérias/classificação , Bactérias/genética , Biodiversidade , Biomarcadores , Doença das Coronárias/metabolismo , Doença das Coronárias/mortalidade , Suscetibilidade a Doenças , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/metabolismo , Especificidade de Órgãos , Índice de Gravidade de Doença
19.
J Assoc Physicians India ; 67(10): 54-56, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31571453

RESUMO

Background: Attention has increasingly turned towards the role of factors, such as inflammation in the development of atherosclerosis and CHD. C-reactive protein (CRP) has emerged as one of the most important novel inflammatory marker. Subsequent risk modification and treatment strategies of CHD keeping on pointer towards inflammation may be the appropriate approach. Aim: The aim of this study was to determine the association of CHD with CRP, a sensitive marker of inflammation. Material and Methods: This is a case control study amongst 300 subjects (150 cases and 150 controls), conducted in the Department of Cardiology at Sri Aurobindo Medical College and P.G Institute, Indore, M.P. Subjects with definite diagnosis of CHD established by coronary angiography (CAG) was taken as cases, subjects matched with age, gender with no conventional risk factor and past history of CHD from the relatives and accompanying persons were enlisted as controls. Results: Estimation of CRP reveals ≥0.6 mg/dl in 88(58.7%) subjects out of 150, compared to 26 (17.3%) control subjects out of 150 which is statistically significant (p value<0.0001) (OR=6.7). Conclusion: CRP as a noble marker of inflammation was significantly higher in subjects of CHD and thus supported adequately the hypothesis of an activation of inflammatory cascade for coronary atheromatous plaque formation and causation of CHD.


Assuntos
Proteína C-Reativa/metabolismo , Doença das Coronárias/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Humanos , Inflamação/metabolismo , Fatores de Risco
20.
Dis Markers ; 2019: 4106293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583028

RESUMO

In this paper, we used tongue coating to obtain metabolites in patients with coronary heart disease (CHD) and chronic renal failure (CRF). The metabolites were analyzed to discover the substance that serves as the underlying basis of the damp phlegm pattern. This analysis is based on the Traditional Chinese Medicine (TCM) theory of "different diseases have the same pattern." The metabolic spectrum was obtained through the Gas Chromatography Mass Spectrometry coupling techniques and analyzed by searching the METLIN and HMDB databases. Some metabolites related to amino acids and glucose metabolism were identified in the tongue-coating samples from damp phlegm pattern patients by comparing them to nondamp phlegm pattern patients and healthy subjects. In addition, there were five common metabolites in the tongue-coating samples from CHD damp phlegm pattern patients compared to CRF damp phlegm pattern patients, which allowed us to understand the theory of "different diseases have the same pattern." In the future, the metabolites identified in this study may be used as noninvasive and convenient biomarkers to distinguish the damp phlegm pattern of CHD and CRF patients.


Assuntos
Doença das Coronárias/diagnóstico , Falência Renal Crônica/diagnóstico , Metaboloma , Língua/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença das Coronárias/metabolismo , Análise Discriminante , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glucose/metabolismo , Humanos , Falência Renal Crônica/metabolismo , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Molhabilidade
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