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1.
PLoS One ; 15(12): e0243800, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315906

RESUMO

Mental disorders (MD) are associated with an increased risk of developing coronary heart disease (CHD) and with higher CHD-related morbidity and mortality. There is a strong recommendation to routinely screen CHD patients for MDs, diagnosis, and treatment by recent guidelines. The current study aimed at mapping CHD patients' (1) state of diagnostics and, if necessary, treatment of MDs, (2) trajectories and detection rate in healthcare, and (3) the influence of MDs and its management on quality of life and patient satisfaction. The design was a cross-sectional study in three settings (two hospitals, two rehabilitation clinics, three cardiology practices). CHD patients were screened for MDs with the Hospital Anxiety and Depression Scale (HADS), and, if screened-positive, examined for MDs with the Structured Clinical Interview for DSM-IV (SCID-I). Quality of Life (EQ-5D), Patient Assessment of Care for Chronic Conditions (PACIC), and previous routine diagnostics and treatment for MDs were examined. Descriptive statistics, Chi-squared tests, and ANOVA were used for analyses. Analyses of the data of 364 patients resulted in 33.8% positive HADS-screenings and 28.0% SCID-I diagnoses. The detection rate of correctly pre-diagnosed MDs was 49.0%. Physicians actively approached approximately thirty percent of patients on MDs; however, only 6.6% of patients underwent psychotherapy and 4.1% medication therapy through psychotherapists/psychiatrists. MD patients scored significantly lower on EQ-5D and the PACIC. The state of diagnostic and treatment of comorbid MDs in patients with CHD is insufficient. Patients showed a positive attitude towards addressing MDs and were satisfied with medical treatment, but less with MD-related advice. Physicians in secondary care need more training inadequately addressing mental comorbidity.


Assuntos
Doença das Coronárias/patologia , Transtornos Mentais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/patologia , Doença das Coronárias/complicações , Estudos Transversais , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Satisfação do Paciente , Psicoterapia , Qualidade de Vida , Índice de Gravidade de Doença
2.
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
3.
Lipids Health Dis ; 19(1): 5, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31926562

RESUMO

BACKGROUND: Real-world evidence of low-density lipoprotein cholesterol (LDL-C) goal attainment rates for Asian patients is deficient. The objective of this study was to assess the status of dyslipidemia management, especially in high-risk patients with cardiovascular disease (CVD) including stroke and acute coronary syndrome (ACS). METHODS: This was a retrospective cohort study of 514,866 subjects from the National Health Insurance Service-National Health Screening Cohort database in Korea. Participants were followed up from 2002 to 2015. Subjects with a high-risk of CVD prior to LDL-C measurement and subjects who were newly-diagnosed for high-risk of CVD following LDL-C measurement were defined as known high-risk patients (n = 224,837) and newly defined high-risk patients (n = 127,559), respectively. Data were analyzed by disease status: stroke, ACS, coronary heart disease (CHD), peripheral artery disease (PAD), diabetes mellitus (DM) and atherosclerotic artery disease (AAD). RESULTS: Overall, less than 50% of patients in each disease category achieved LDL-C goals (LDL-C < 70 mg/dL in patients with stroke, ACS, CHD and PAD; and LDL-C < 100 mg/dL in patients with DM and AAD). Statin use was observed in relatively low proportions of subjects (21.5% [known high-risk], 34.4% [newly defined high-risk]). LDL-C goal attainment from 2009 to 2015 steadily increased but the goal-achiever proportion of newly defined high-risk patients with ACS remained reasonably constant (38.7% in 2009; 38.1% in 2015). CONCLUSIONS: LDL-C goal attainment rates in high-risk patients with CVD and DM in Korea demonstrate unmet medical needs. Proactive management is necessary to bridge the gap between the recommendations of clinical guidelines and actual clinical practice.


Assuntos
Aterosclerose/sangue , LDL-Colesterol/sangue , Doença das Coronárias/sangue , Diabetes Mellitus/sangue , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/patologia , Idoso , Aterosclerose/patologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Doença das Coronárias/patologia , Diabetes Mellitus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/patologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/patologia
4.
Mol Med Rep ; 21(1): 151-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746393

RESUMO

It has been universally acknowledged that interleukin­37 (IL­37) has an immunosuppressive effect on various inflammatory disorders. However, whether IL­37 participates in the acute inflammation associated with coronary heart disease (CHD) has not yet been clarified. In the present study, the association between the serum levels of IL­37 and the clinical indexes of CHD were analysed. In addition, the anti­inflammatory effects of IL­37 on peripheral blood mononuclear cells (PBMCs) were studied in CHD patients. PBMCs from 46 healthy controls (HCs) and 92 CHD patients were cultured in vitro and stimulated using the recombinant IL­37 protein. The protein levels, as well as the mRNA expression of inflammatory cytokines (TNF­α, IL­1ß, IL­6, and IL­17) were analysed by enzyme­linked immunosorbent assay (ELISA) and real­time polymerase chain reaction (RT­PCR). Spearman's correlation test was performed to examine the association between the serum level of IL­37 and the levels of pro­inflammatory cytokines, certain clinical indexes, and disease activity during CHD. Compared to the HCs, the CHD patients, especially those with acute myocardial infarction, exhibited higher levels of IL­37 in their PBMCs and sera. Serum levels of IL­37 were associated with the levels of IL­17, IL­6, and TNF­α, and clinical indexes such as the left ventricular ejection fraction (LVEF), amino­N­terminal pro­plasma brain natriuretic peptide (NT­proBNP) levels, and cardiac troponin T (cTnT) levels in CHD patients. Compared to the HC group, the production of inflammatory cytokines such as IL­17, IL­6, TNF­α, and IL­1ß increased in the PBMCs of CHD patients and significantly decreased after the stimulation of the cells with recombinant IL­37. The IL­37 levels in CHD patients were high, and were correlated with the levels of CHD­related pro­inflammatory cytokines and disease activity. Notably, the expression of CHD­related pro­inflammatory cytokines in the PBMCs of CHD patients decreased following the stimulation of the cells with recombinant IL­37, indicating that IL­37 exerts anti­inflammatory effects during CHD.


Assuntos
Doença das Coronárias/sangue , Interleucina-1/sangue , Leucócitos Mononucleares/metabolismo , Idoso , Doença das Coronárias/patologia , Doença das Coronárias/prevenção & controle , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Inflamação/prevenção & controle , Interleucina-1/farmacologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/farmacologia
5.
Georgian Med News ; (308): 47-52, 2020 Nov.
Artigo em Russo | MEDLINE | ID: mdl-33395640

RESUMO

Purpose - to assess the probability of occurrence of the main cardiovascular events in the patients after revascularization interventions with a combined course of a stable coronary heart disease and non-alcoholic steatohepatitis (NASH) by indicators of fibrogenesis. 164 patients with stable coronary heart disease were observed, including: 54 patients with NASH (a main group); 110 patients without NASH (a comparison group). All patients underwent general clinical examination, electrocardiography, coronary angiography, echocardiography, assessment of liver function, markers of fibrosis and long-term prognosis by the Kaplan-Meier method. It was found that the patients with stable coronary heart disease, combined with NASH, are characterized by the fibrosis progression, that is characterized by a significantly high value of fibrogenesis markers. The presence of NASH in patients with stable coronary heart disease causes a worsening of the disease and forms a negative prognosis in such patients in a two-year term. The prognosis of the patients who underwent coronary artery stenting depends on the course of non-alcoholic fatty liver disease and is the most prognostically unfavorable against the combination of the FIB-4 index ≥2.0 and NASH.


Assuntos
Doença das Coronárias , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Doença das Coronárias/complicações , Doença das Coronárias/diagnóstico , Doença das Coronárias/patologia , Fibrose , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia , Prognóstico
6.
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
8.
Undersea Hyperb Med ; 46(5): 581-601, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31683356

RESUMO

Introduction: We aimed to document identified cases of immersion pulmonary edema (IPE) in divers from Oceania (the Indo-Pacific region) from January 2002 to May 2018, inclusive. Method: Cases were identified using various sources, including searches of the Divers Alert Network Asia-Pacific (DAN AP) Fatality Database, published case reports, and interviews with survivors who had reported their incident to DAN AP. Where available, investigations, pathology and autopsy results were obtained. Only incidents diagnosed as IPE by diving physicians or pathologists with experience in the investigation of diving accidents were included. Individual case histories and outcomes, together with brief individual summaries of the associations and possible contributing factors were recorded. Results: Thirty-one IPE incidents in divers from Oceania were documented. There were two surface snorkelers, 22 scuba air divers and seven nitrox divers which included three closed-circuit rebreathers (CCR). The mean (SD) age was 53 (12) years, 58% of victims were females, and the average dive profile was to a maximum depth of 19 meters of seawater for 25 minutes. Six victims (19%) had previous episodes of IPE. There were nine recorded fatalities. Cardiac anomalies dominated the associated or possible contributing factors. These included valvular disease in 29%, transient cardiomyopathies in 26% and dysrhythmias in 16%. Conclusions: Previously reported associations of IPE such as exertion, stress, cold exposure, negative inspiratory pressure, hypertension, overhydration, ascent or surfacing, tight wetsuit, aspiration and certain medications were identified. Cardiac conditions were frequent and included chronic disorders (valvular pathology, coronary artery disease) and transient disorders (dysrhythmias, transient myocardial dysfunction, takotsubo or stress cardiomyopathy). It is likely that the chronic cardiac disorders may have contributed to the IPE, whereas the transient cases could be either sequelae, contributors or coincidental to the IPE.


Assuntos
Mergulho/efeitos adversos , Edema Pulmonar/etiologia , Adulto , Idoso , Autopsia , Doença das Coronárias/patologia , Suscetibilidade a Doenças/etiologia , Suscetibilidade a Doenças/patologia , Evolução Fatal , Feminino , Cardiopatias/complicações , Humanos , Imersão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oceania/epidemiologia , Esforço Físico , Edema Pulmonar/diagnóstico , Edema Pulmonar/epidemiologia , Edema Pulmonar/patologia , Fatores de Risco , Água do Mar , Distribuição por Sexo , Natação , Cardiomiopatia de Takotsubo/complicações , Adulto Jovem
9.
Pharmacogenomics ; 20(16): 1143-1150, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31617441

RESUMO

Niacin (nicotinic acid) is a potent lipid-lowering agent that has been used for prevention of coronary heart disease. Niacin activates the HCAR2 receptor found on adipocytes, macrophages and various immune cells throughout the body. Activation of the HCAR2 receptor by niacin results in beneficial anti-inflammatory effects that are independent of lipid lowering. This review summarizes the use of niacin in treatment of dyslipidemia, the pharmacogenetics of niacin response and the potential role of HCAR2 signaling in the treatment of a variety of inflammatory and metabolic diseases.


Assuntos
Doença das Coronárias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Niacina/farmacologia , Receptores Acoplados a Proteínas-G/genética , HDL-Colesterol/genética , Doença das Coronárias/genética , Doença das Coronárias/patologia , Genótipo , Humanos , Hipolipemiantes/efeitos adversos , Lipídeos/antagonistas & inibidores , Lipídeos/genética , Niacina/efeitos adversos , Polimorfismo de Nucleotídeo Único
10.
Indian J Med Res ; 150(1): 43-49, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31571628

RESUMO

Background & objectives: Brain-derived neurotrophic factor (BDNF) facilitates neuronal survival, differentiation and synaptic connectivity and affects neurotransmission throughout the brain. However, it has also a modulatory role in energy homeostasis, obesity and cardiovascular function. Obesity, high body mass index (BMI) and dyslipidaemia, among other factors, contribute to coronary heart disease (CHD) development. The exact role of BDNF in development of CHD is not well defined. This study was aimed to evaluate if plasma BDNF concentration was associated with CHD in ethnically homogeneous groups of patients and to correlate plasma BDNF levels with known risk factors for CHD. Methods: Plasma BDNF concentration, BDNF Val66Met polymorphism and other biological and anthropological risk factors for CHD were determined in 208 patients with CHD and 156 healthy controls. Results: Plasma BDNF concentration was significantly (P <0.01) reduced in patients with CHD compared to controls, and it was not influenced by gender, age, smoking or BDNF Val66Met polymorphism. It was considerably correlated with cholesterol (P=0.004), low-density lipoprotein (P=0.006), and diastolic blood pressure (P=0.018) in patients with CHD and with platelet number (P=0.003) in healthy controls. Interpretation & conclusions: The results revealed lower plasma BDNF concentration in patients with CHD, suggesting that decreased plasma BDNF concentration might be associated with CHD pathogenesis. Longitudinal studies with a large sample need to be conducted to confirm these findings.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Doença das Coronárias/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Doença das Coronárias/patologia , Dislipidemias/epidemiologia , Dislipidemias/genética , Dislipidemias/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo Único/genética
11.
Biosci Rep ; 39(9)2019 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31501353

RESUMO

The aim of the present study was to investigate the role of miR-31 in Th22 differentiation in coronary heart disease (CHD). Th22 frequencies in peripheral blood of CHD patients and controls as well as in CD4+ T cells were detected by flow cytometry. The mRNA expression of Th22-associated transcription factor aryl hydrocarbon receptor (AHR) and Th22-effector cytokine interleukin (IL)-22, as well as miR-31 were examined by quantitative real-time PCR (qRT-PCR). The protein level of BTB domain and CNC homolog 2 (Bach2) was measured by Western blotting. The interaction between miR-31 and Bach2 was verified using dual luciferase reporter assay. The results showed that Th22 frequency and miR-31 expression were elevated in CHD patients. Furthermore, miR-31 mimic and Bach2 silencing significantly promoted Th22 frequency and the levels of AHR and IL-22 in CD4+ T cells from CHD patients. Further studies showed that miR-31 facilitated Th22 cell differentiation by targeting and inhibiting Bach2. Our data indicate that miR-31 promotes Th22 differentiation through targeting Bach2 in CHD.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/sangue , Doença das Coronárias/sangue , Interleucinas/sangue , MicroRNAs/sangue , Fatores de Transcrição Hélice-Alça-Hélice Básicos/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular/genética , Doença das Coronárias/imunologia , Doença das Coronárias/patologia , Feminino , Regulação da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica , Receptores de Hidrocarboneto Arílico/sangue , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia
12.
Pharmacogenomics ; 20(14): 1021-1031, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31559922

RESUMO

Aim: To explore the association of APOE polymorphism (rs7412:526C>T and rs429358:388T>C) with glucose, lipid and serum uric acid (UA) metabolism in patients with hypertension or coronary heart disease (CHD). Methods: A total of 544 patients with hypertension or CHD were selected for this study from March 2017 to January 2018. According to the APOE genotypes (excluding the E2/E4 genotype), the subjects were divided into three groups (E2/E2+E2/E3 genotypes, E3/E3 genotype [the wild-type] and E3/E4+E4/E4 genotypes) and the difference of metabolism among the three groups was compared. Results: There were significant differences in total cholesterol (TC), triglycerides, low-density lipoprotein (LDL), high-density lipoprotein and serum UA levels among the three groups. Compared with APOE E3 homozygote, APOE E4 carriers possessed higher TC, triglycerides and LDL levels, whereas APOE E2 carriers had higher high-density lipoprotein level, lower TC and LDL levels. Furthermore, multivariate logistic regression analysis found that setting E3/E3 genotype as the reference group, the carriers of APOE E4 allele (E3/E4+E4/E4 genotypes) were significantly related to hypertriglyceridemia, and APOE E2 allele (E2/E2+E2/E3 genotypes) was significantly correlated with hyperuricemia. Conclusion: APOE polymorphism was associated with blood lipid and serum UA metabolism in patients with hypertension or CHD. Compared with APOE E3 homozygote, APOE E4 allele was related to elevated triglycerides, and APOE E2 allele was correlated with increased serum UA level.


Assuntos
Apolipoproteínas E/genética , Doença das Coronárias/genética , Predisposição Genética para Doença , Hipertensão/genética , Idoso , Doença das Coronárias/sangue , Doença das Coronárias/patologia , Feminino , Estudos de Associação Genética , Humanos , Hipertensão/sangue , Hipertensão/patologia , Lipídeos/sangue , Lipídeos/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Ácido Úrico/sangue
13.
Mol Genet Genomic Med ; 7(11): e955, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31496134

RESUMO

BACKGROUND: Coronary heart disease (CHD) is one of the most severe cardiovascular diseases. Cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) is a significant susceptibility locus for cardiovascular disease by regulating inflammation response and cell cycle. The aim of this study was to assess whether CDKN2B-AS1 polymorphisms are associated with CHD risk in the Chinese Han population. METHODS: A total of 501 CHD patients and 496 healthy controls were recruited from Central South University Xiangya School of Medicine Affiliated Haikou Hospital, five CDKN2B-AS1 polymorphisms (rs10115049, rs75227345, rs2383205, rs10738606, and rs1333049) were analyzed by the Agena MassARRAY platform. The association of CDKN2B-AS1 polymorphisms and CHD risk was determined by odd ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: CDKN2B-AS1 rs10738606 was significantly associated with CHD under codominant (p = .03), dominant (p = .019), recessive (p = .010), additive (p = .003), and allele (p = .003) models. Gender-based subgroup tests showed that four polymorphisms (rs75227345, rs2383205, rs10738606 and rs1333049) were associated with CHD in males (p < .05). And age-based subgroup tests indicated that rs2383205 and rs10738606 were associated with CHD among individuals, respectively (p < .05). For CHD patients, rs1333049 decreased the risk of diabetes under heterozygote (p = .014) and dominant (p = .024) models. CONCLUSIONS: In conclusion, CDKN2B-AS1 polymorphisms were associated with CHD risk in the combined or subgroup tests, suggesting an important role of CDKN2B-AS1 in CHD susceptibility.


Assuntos
Doença das Coronárias/genética , Doença das Coronárias/patologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco
14.
J Mol Cell Cardiol ; 136: 27-41, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31505198

RESUMO

Coronary heart disease (CHD) is a common heart disease and the leading cause of cardiovascular death. Apoptosis and autophagy are two forms of programmed cell deaths which participate in the pathogenesis, development and prognosis of CHD. They are activated by several different pathways respectively and can interact with each other through the Beclin 1-Bcl-2/Bcl-xL complex, mTOR, TRAIL, TNF-α, ER stress and nucleus p53 pathways. Excessive apoptosis can promote myocardial ischemia, ischemia/reperfusion (I/R) injury, post-ischemia cardiac remodeling and coronary atherosclerosis except for VSMC-induced atherosclerosis progress. In contrast, activated autophagy protects heart from myocardial ischemia injury and post-ischemia cardiac remodeling, but can exert controversial effects on I/R injury and coronary atherosclerosis. Therefore, considering the pathological significance and mechanisms of apoptosis and autophagy underlying CHD, therapeutic implication of targeting apoptosis and autophagy is obvious. Fortunately, some therapeutic drugs and pharmacologic compounds involving mTOR inhibitor and AMPK activator have been reported to regulate apoptosis and autophagy. Although recent studies are limited and insufficient, they have pointed out the complex interplay between apoptosis and autophagy and further provided treatment concept for CHD by balancing the switch between the two responses.


Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , Doença das Coronárias/metabolismo , Doença das Coronárias/patologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença das Coronárias/terapia , Estresse do Retículo Endoplasmático , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patologia
15.
Pathol Res Pract ; 215(9): 152512, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31296440

RESUMO

Coronary heart disease (CHD) is one of the main risks of death, which is mainly caused by coronary arteries arteriosclerosis. The present study aims to investigate the potential roles of miR-17 in CHD. In the present study, Human umbilical vascular endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL). qRT-PCR and western blot were used to examine the mRNA and protein levels, respectively. CCK-8 and flow cytomtry were conducted to determine the proliferation and apoptosis of ox-LDL treated HUVECs. Moreover, luciferase assay was performed to confirm whether insulin-like Growth Factor-1 (IGF-1) was a target of miR-17. The results showed that miR-17 was upregulated in ox-LDL treated HUVECs, while IGF-1 was downregulated. The luciferase activity of ox-LDL treated HUVECs was decreased after the treatment of miR-17 mimics and IGF-1 3'UTR WT. Moreover, overexpressed miR-17 promoted the cell viability and inhibited the apoptosis of ox-LDL treated HUVECs, which was more potent after the treatment of IGF-1 siRNA. Furthermore, the expression of Bax and Caspase3 was decreased, and Bcl-2 was increased in ox-LDL treated HUVECs transfected with miR-17 mimics, which was further decreased after transfection with IGF-1 siRNA. Taken together, miR-17 may regulate the proliferation and apoptosis of ox-LDL treated HUVECs. miR-17 may be a promising biomarker for CHD.


Assuntos
Doença das Coronárias/metabolismo , Doença das Coronárias/patologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , MicroRNAs/metabolismo , Apoptose/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Lipoproteínas LDL/toxicidade
16.
Mol Med Rep ; 20(2): 1826-1836, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257469

RESUMO

Nucleotide­binding oligomerization domain, leucine rich repeat, and pyrin domain­containing protein 3 (NLRP3) inflammasome has been implicated in a series of physiological and pathological processes. However, its correlation in coronary heart disease (CHD) still remains to be elucidated. The present study aimed to determine the expression of NLRP3 inflammasome in peripheral blood monocytes (PBMCs) of stable angina pectoris (SAP) and acute myocardial infarction (AMI) patients. In addition, the effect of rosuvastatin on their activities was analyzed in vitro. A total of 60 participants with SAP (n=20), AMI (n=20) and non­CHD controls (n=20) were enrolled. Fluorescence­activated cell sorting, real­time PCR, western blotting and enzyme­linked immunosorbent assay were performed to reveal the role of NLRP3 inflammasome. NLRP3 inflammasome was expressed in the PBMCs, and revealed an increased expression along the downstream interleukin (IL)­1ß and IL­18 in both SAP and AMI groups, compared to the control group. Moreover, there was a more marked increase in the expression of these indicators in AMI patients when compared to SAP patients. Interference with rosuvastatin in vitro revealed that the expression of NLRP3 inflammasome and its downstream cytokines were significantly downregulated in both SAP and AMI groups in a time­dependent manner. The activation of NLRP3 inflammasome may be involved in the development of CHD, and rosuvastatin could attenuate the inflammatory process of atherosclerosis by downregulating NLRP3 expression and its downstream mediators. These findings indicated a potential role of NLRP3 in the pathogenesis and management of CHD, and also provided new insights into the mechanistic framework of rosuvastatin activity.


Assuntos
Angina Estável/sangue , Doença das Coronárias/sangue , Infarto do Miocárdio/sangue , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Rosuvastatina Cálcica/administração & dosagem , Idoso , Angina Estável/tratamento farmacológico , Angina Estável/patologia , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/genética , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Transdução de Sinais/efeitos dos fármacos
17.
Lipids Health Dis ; 18(1): 134, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31170997

RESUMO

Low-density lipoprotein cholesterol (LDL-C) has been recommended as the primary treatment target on lipid management in coronary heart disease (CHD) patients for past several decades. However, even by aggressive LDL-C lowering treatment, patients still present a significant residual risk of major adverse cardiovascular events (MACE). Non-high-density lipoprotein cholesterol (non-HDL-C) contained all the atherogenic lipoproteins, such as chylomicron, very-low density lipoprotein (VLDL), LDL, intermediate density lipoprotein (IDL). Many prospective observation studies have found that non-HDL-C was better than LDL-C in predicting risks of MACE. Since non-HDL-C appears to be superior for risk prediction beyond LDL-C, current guidelines have emphasize the importance of non-HDL-C for guiding cardiovascular prevention strategies and have flagged non-HDL-C as a co-primary therapeutic target. The goals of non-HDL-C were recommended as 30 mg/dl higher than the corresponding LDL-C goals, but the value seemed inappropriate. This review provide evidence for changing lipid management strategy to focus on non-HDL-C and appropriate values for adding to LDL-C goals would be proposed.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Quilomícrons/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/prevenção & controle , HDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/antagonistas & inibidores , Doença das Coronárias/complicações , Doença das Coronárias/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/antagonistas & inibidores , Lipídeos/genética , Fatores de Risco
18.
Curr Drug Targets ; 20(15): 1517-1536, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215391

RESUMO

Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extraterminal family. BRD4 inhibitors can regulate acetylated lysine and form protein complexes that initiate transcriptional programs as an epigenetic regulator of the histone code. BRD4 was initially considered to be one of the most promising targets for combating malignant tumors. However, many recent studies have shown that BRD4 plays a crucial role in various kinds of diseases, including cancer, coronary heart disease, neurological disorder, and obesity. Currently, several BRD4 inhibitors are undergoing clinical trials. A search for new BRD4 inhibitors appears to be of great utility for developing novel drugs. In this mini-review, we highlight the inhibitors of BRD4 from natural products and synthesized sources, as well as their applications in cancer, glucolipid metabolism, inflammation, neuronal stimulation activation, human immunodeficiency virus and renal fibrosis.


Assuntos
Produtos Biológicos/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Descoberta de Drogas , Terapia de Alvo Molecular/métodos , Fatores de Transcrição/antagonistas & inibidores , Acetilação/efeitos dos fármacos , Produtos Biológicos/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/patologia , Glicolipídeos/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/patologia , Obesidade/tratamento farmacológico , Obesidade/patologia , Fatores de Transcrição/metabolismo
19.
J Cell Physiol ; 234(12): 22921-22934, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31148189

RESUMO

Bax triggers cell apoptosis by permeabilizing the outer mitochondrial membrane, leading to membrane potential loss and cytochrome c release. However, it is unclear if proteasomal degradation of Bax is involved in the apoptotic process, especially in heart ischemia-reperfusion (I/R)-induced injury. In the present study, KPC1 expression was heightened in left ventricular cardiomyocytes of patients with coronary heart disease (CHD), in I/R-myocardium in vivo and in hypoxia and reoxygenation (H/R)-induced cardiomyocytes in vitro. Overexpression of KPC1 reduced infarction size and cell apoptosis in I/R rat hearts. Similarly, the forced expression of KPC1 restored mitochondrial membrane potential (MMP) and cytochrome c release driven by H/R in H9c2 cells, whereas reducing cell apoptosis, and knockdown of KPC1 by short-hairpin RNA (shRNA) deteriorated cell apoptosis induced by H/R. Mechanistically, forced expression of KPC1 promoted Bax protein degradation, which was abolished by proteasome inhibitor MG132, suggesting that KPC1 promoted proteasomal degradation of Bax. Furthermore, KPC1 prevented basal and apoptotic stress-induced Bax translocation to mitochondria. Bax can be a novel target for the antiapoptotic effects of KPC1 on I/R-induced cardiomyocyte apoptosis and render mechanistic penetration into at least a subset of the mitochondrial effects of KPC1.


Assuntos
Doença das Coronárias/genética , Mitocôndrias/genética , Complexos Ubiquitina-Proteína Ligase/genética , Proteína X Associada a bcl-2/genética , Animais , Apoptose/genética , Hipóxia Celular/genética , Sobrevivência Celular/genética , Doença das Coronárias/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Humanos , Potencial da Membrana Mitocondrial/genética , Mitocôndrias/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteólise , Ratos , Transdução de Sinais/genética
20.
Biomed Res Int ; 2019: 5046867, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31198785

RESUMO

Coronary heart disease (CHD) is one of the most common causes of death in the world. Numerous studies have shown that as the degree of atherosclerotic disease increases, leukocyte telomere length gradually decreases. Short telomeres increase the risk of all-cause death and cardiovascular death. However, the reported results are not consistent, since the experimental design method, the measurement method, and the disease outcome are different. Therefore, we searched five major literature databases (Pubmed, Web of science, Embase, CNKI, and Wangfang) and finally included 18 eligible articles (including 5,150 patients with CHD and 9341 controls). We found that telomere length in patients with CHD was significantly shorter than that in controls, and the telomere length was inversely correlated with the severity of CHD. Subgroup analysis showed that telomere shortening was the most significant in Asian patients with CHD, in CHD patients with an average age <65 years, and in men with CHD. The mechanism of shortening the telomere length leading to the occurrence and development of CHD is worthy of further study.


Assuntos
Doença das Coronárias/metabolismo , Encurtamento do Telômero , Telômero/metabolismo , Doença das Coronárias/patologia , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Telômero/patologia
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