RESUMO
Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.
RESUMO
Atherosclerosis is a common comorbidity of type II diabetes and a leading cause of death worldwide. The presence of oxidized low-density lipoprotein (ox-LDL) drives atherogenesis by inducing oxidative stress, mitochondrial dysfunction, expression of proinflammatory cytokines and chemokines including interleukin (IL)-1ß, IL-6, and monocyte chemoattractant protein 1 (MCP-1), adhesion molecules including vascular cellular adhesion molecule 1 (VCAM-1) and E-selectin, and downregulating expression of the Krüppel-like factor 2 (KLF2) transcription factor. Importantly, ox-LDL induced the attachment of THP-1 monocytes to endothelial cells. In the present study, we demonstrate for the first time that the specific glucagon-like peptide 1 receptor (GLP-1R) agonist dulaglutide may prevent these atherosclerotic effects of ox-LDL by preventing suppression of KLF2 by p53 protein in human aortic endothelial cells. KLF2â¯has been shown to play a major role in protecting vascular endothelial cells from damage induced by ox-LDL and oscillatory shear, and therefore, therapies capable of mediating KLF2 signaling may be an attractive treatment option for preventing the development and progression of atherosclerosis.
Assuntos
Aterosclerose/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Fragmentos Fc das Imunoglobulinas/farmacologia , Lipoproteínas LDL/metabolismo , Monócitos/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Aterosclerose/metabolismo , Adesão Celular , Células Cultivadas , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliais , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos Semelhantes ao Glucagon/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
The purpose of this study is to test the efficacy of bioactive natural product berberine in the treatment of patients with atrial fibrillation (AF). Data of 45 paroxysmal AF patients treated with berberine and 43 age, gender, New York Heart Association functional classification score, and concomitant cardiovascular disease matched patients treated with amiodarone were analyzed retrospectively to examine conversion rate, average conversion time, average heart rate, and echocardiographic parameters. There was no statistical difference between berberine and amiodarone on conversion rate or echocardiographic parameters. Berberine treatment showed a significantly longer average time to conversion and higher heart rate during sinus rhythm (SR) than amiodarone. Echocardiographic parameters showed that E/A ratio and left atrial diameter were significantly improved after 6- and 12-month berberine treatment, but only E/A ratio improved significantly at the same time points after amiodarone treatment. This is the first report to specifically compare efficacy of berberine and amiodarone in the treatment of patients with AF. We find that berberine and amiodarone are equally effective for conversion of AF and maintenance of normal SR.
Assuntos
Antiarrítmicos/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Berberina/administração & dosagem , Idoso , Antiarrítmicos/química , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Berberina/química , Produtos Biológicos/administração & dosagem , Produtos Biológicos/química , Ecocardiografia Tridimensional , Cardioversão Elétrica , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/patologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model. METHODS: Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting. RESULTS: After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups. CONCLUSIONS: Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.
Assuntos
Anti-Hipertensivos/farmacologia , Aterosclerose/patologia , Hiperuricemia/complicações , Losartan/farmacologia , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Aterosclerose/etiologia , Western Blotting , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Imuno-Histoquímica , Lipoproteínas LDL , Masculino , Microscopia Eletrônica de Transmissão , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ácido Úrico/sangue , Ácido Úrico/metabolismoRESUMO
OBJECTIVE: To compare the efficacy and safety of 5 mg perindopril arginine salt and 4 mg perindopril tert-butylamine salt for patients with mild to moderate essential hypertension. METHODS: The study was designed as multicenter, randomized, double-blind, active controlled trial with two parallel groups enrolling 524 participants with mild to moderate essential hypertension. After 2-week run-in period, 186 patients were enrolled and randomly treated with 5 mg perindopril arginine salt and 183 patients were enrolled and randomly treated with 4 mg perindopril tert-butylamine salt. The random sequence was generated by the I.R.I.S., and a balance was made in each center. After double-blind treatment for 8 weeks, the dose could be doubled for patients with uncontrolled BP ((SBP) ≥ 140 mmHg (1 mmHg = 0.133 kPa) or diastolic blood pressure (DBP) ≥ 90 mmHg) and patients were treated for another 4 weeks. RESULTS: The sitting SBP was similarly decreased by (19.9 ± 17.2) mmHg in perindopril arginine group and (18.5 ± 14.7) mmHg (P = 0.000 5) in perindopril tert-butylamine group post 8 weeks treatment. Dose was doubled in 109 patients (59.9%) in perindopril arginine group and 116 patients (63.7%) in perindopril tert-butylamine group. At 12 weeks post therapy, the sitting SBP decreased by (19.8 ± 16.2) and (19.6 ± 16.3) mmHg respectively in the 2 groups. The decrease of sitting DBP was also similar in both groups (-12.0 ± 10.0) mmHg and (-11.0 ± 8.9) mmHg (P < 0.000 1), respectively. The control rate or response rate was also similar between the two groups (control rate over 8 weeks was 38.5% vs. 31.3%, 95% CI (-2.6-16.9), control rate over 12 weeks was 36.3% vs. 35.7%, 95% CI (-9.3-10.4), response rate over 8 weeks was 64.3% vs. 63.2%, 95% CI (-8.8-11.0), response rate over 12 weeks was 65.9% vs. 64.8%, 95% CI (-8.7-10.9)). Incidence of adverse events was low and similar in both therapy groups. CONCLUSIONS: The results show that perindopril arginine salt 5 mg is as efficient as perindopril tert-butylamine 4 mg on lowering BP for patients with mild to moderate essential hypertension. Both drugs have good safety profile and are well tolerated by patients in this cohort.
Assuntos
Hipertensão , Anti-Hipertensivos , Arginina , Pressão Sanguínea , Butilaminas , Método Duplo-Cego , Hipertensão Essencial , Humanos , Perindopril , Cloreto de SódioRESUMO
OBJECTIVE: To investigate whether rs12731181 (AâG) interrupted miR-590-3p-mediated suppression of the prostaglandin F2α receptor (FP) and whether it is associated with essential hypertension in the Chinese population. APPROACH AND RESULTS: We found that miR-590-3p regulates human FP gene expression by binding to its 3'-untranslated region. rs12731181 (AâG) altered the binding affinity between miR-590-3p and its FP 3'-untranslated region target, thus reducing the suppression of FP expression, which, in turn, enhanced FP receptor-mediated contractility of vascular smooth muscle cells. Overexpression of FP augmented vascular tone and elevated blood pressure in mice. An association study was performed to analyze the relationship between the FP gene and essential hypertension in the Han Chinese population. The results indicated that the rs12731181 G allele was associated with susceptibility to essential hypertension. Carriers of the AG genotype exhibited significantly higher blood pressure than those of the AA genotype. FP gene expression was significantly higher in human peripheral leukocytes from individuals with the AG genotype than that in leukocytes from individuals with the AA genotype. CONCLUSIONS: rs12731181 in the seed region of the miR-590-3p target site is associated with increased risk of essential hypertension and represents a new paradigm for FP involvement in blood pressure regulation.
Assuntos
Povo Asiático/genética , Hipertensão/genética , MicroRNAs/genética , Receptores de Prostaglandina/genética , Regiões 3' não Traduzidas , Animais , Sítios de Ligação , China/etnologia , Hipertensão Essencial , Predisposição Genética para Doença , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Transcrição GênicaRESUMO
The purpose of the study was to probe the therapeutic effect of baicalin on immunosuppression in the mouse model of cecal ligation and puncture (CLP)-induced sepsis. Mouse model was established by employing the procedure of CLP. The proliferation of T lymphocytes was measured using CFDA-SE staining and MTT method, and the proliferation index was determined to assess the proliferation status of the outer peripheral and mesenteric cells of the lymph node in various treatment groups. Griess reagent was used to detect serum NO concentrations. The CLP mice treated with baicalin showed reduced mortality and improved physical appearance as compared to the untreated animals. The locomotion and coat color of the baicalin-treated mice were normal compared to those of untreated CLP mice. Additionally, upon dissecting, only little abscess and adhesions were observed in their peritoneal cavity. The atrophy of thymus gland and spleen in the septic mice was significantly ameliorated in baicalin-treated CLP mice. Baicalin also suppressed the serum NO levels and promoted the proliferation of peripheral lymphocytes in CLP mice. Baicalin reduced the mortality in septic mice, exhibiting a thymus gland and spleen protecting effect. The results suggest that baicalin mediated its protective effect against CLP-induced sepsis by inhibiting T lymphocytes apoptosis and serum NO concentrations.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Flavonoides/uso terapêutico , Sepse/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Flavonoides/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sepse/imunologia , Baço/efeitos dos fármacos , Timo/efeitos dos fármacosRESUMO
OBJECTIVE: Here we develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of digoxin in serum. DESIGN AND METHODS: The serum samples were extracted with methyl tert-butyl ether using an isotope-labeled digoxin-d3 as internal standard. The analyte was separated on a reverse phase Capcell C18 column and detected in positive electrospray ionization multiple reaction monitoring mass spectrometry. RESULTS: The chromatographic analysis was carried out within 3 min, but the complete analysis took longer because of the liquid-liquid extraction. The lower limit of quantification was 0.1 ng/mL for digoxin. The intra- and inter-batch precisions were less than 12%, and the bias ranged from -9.1% to 10.7%. The external quality assessment (EQA) results obtained with the LC-MS/MS method were comparable to target values. Subsequently, this method has been applied to the therapeutic monitoring of digoxin in a clinical setting. CONCLUSION: In this study, we have developed a rapid and reliable LC-MS/MS method for the therapeutic monitoring of digoxin in human serum.