Cardiotrophin-1 Levels Research Articles

The role of Cardiotrophin-1 and echocardiography in early detection of subclinical diabetic cardiomyopathy in children and adolescents with type 1 diabetes mellitus.

To assess the role of Cardiotrophin-1 (CT-1) and echocardiography in early detection of subclinical Diabetic Cardiomyopathy (DCM) in children with type 1 Diabetes Mellitus (T1D). This case-control study included two groups of children and adolescents aged between 7 and 18. Group (1) included forty patients with T1D (duration > 5 years) regularly followed at the children's hospital of Cairo University, and Group (2) included forty age and sex-matched healthy subjects as a control group. The serum level of CT-1 was measured, and conventional echocardiography, tissue Doppler imaging (TDI), and 2D speckle tracking echocardiography were performed. The level of CT-1 in the cases ranged from 11 to 1039.4 pg/ml with a median (IQR) of 19.4 (16.60-25.7) pg/ml, while its level in the control group ranged from 10.8 to 162.6 pg/ml with a median (IQR) of 20.2 (16.2-24.8) pg/ml. CT-1 levels showed no statistically significant difference between cases and controls. Patients had significantly higher mean left ventricle E/E' ratio (p<0.001), lower mean 2D global longitudinal strain (GLS) of the left ventricle (LV) (p<0.001), and lower mean GLS of the right ventricle (RV) (p<0.001) compared to controls. Ofpatients with diabetes, 75 % had LV diastolic dysfunction, 85 % had RV diastolic dysfunction, 97.5 % had LV systolic dysfunction, and 100 % had RV systolic dysfunction. Non-conventional echocardiography is important for early perception of subclinical DCM in patients with T1D. CT-1 was not specific for early detection of DCM.

DEPENDENCE OF CARDIOTROPHIN-1 ON BIOCHEMICAL AND HORMONAL FACTORS IN PATIENTS WITH COMORBID PATHOLOGY: ARTERIAL HYPERTENSION, DIABETES MELLITUS TYPE 2 AND OBESITY

The prevalence of arterial hypertension, type 2 diabetes mellitus (type 2 DM), and obesity is constantly increasing worldwide. Today, a complex of factors, which primarily include chronic emotional stress, pandemics of infectious diseases, military conflicts, have led to a significant increase in chronic non-communicable diseases. The aim of the study. To determine the dependence of Cardiotrophin-1 on a number of biochemical and hormonal indicators in patients with arterial hypertension, type 2 DM, and obesity, representatives of the Ukrainian population. Materials and methods. The study included 211 patients aged 49 to 65 years, who were divided into groups depending on the pathology: patients with arterial hypertension – 49 persons, Group I; patients with arterial hypertension in combination with class 1 obesity – 54 persons, Group 2; patients with arterial hypertension in combination with type 2 DM – 57 persons, Group 3; patients with arterial hypertension, type 2 DM, class 1 obesity – 51 persons, Group 4; as well as 20 persons – the Control group. Determination of the content of Cardiotrophin-1, catestatin, leptin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), N-terminal brain natriuretic peptide (NT-proBNP), 25-OH of common vitamin D (Vitamin D3), blood levels was carried out by enzyme immunoassay on Labline-90 analyzer (Austria), using commercial test systems manufactured by FineTest (ELISA, China), BT LAB (ELISA, China), DBC (ELISA, China), Elabscience (ELISA, Canada), Monobind Inc. (ELISA, USA). Statistical data analysis was performed, using the statistical software package Statistica, 12 (Stat Soft Inc, USA), Microsoft Office Excel 2013. Data are shown as mean (M) and standard deviations (δ). An error of less than 5% was considered to be significant (p&lt;0.05). Stepwise regression analysis was used to determine the extent of exposure of the studied indicators to the CTF-1 level, with its effectiveness assessed by one-way analysis of variance (ANOVA). Results. Thus, the study indicates that comorbid patients with arterial hypertension, type 2 DM, and obesity are predicted to develop complications from the cardiovascular system and Cardiotrophin-1 is a marker of their development. In the examined patients as a whole, the level of Cardiotrophin-1 is closely related to the peptide-hormonal complex: catestatin, leptin, cystatin C, brain natriuretic peptide, and lipocalin associated with neutrophil gelatinase. Conclusions: The serum concentration of Cardiotrophin-1 in patients with arterial hypertension increases significantly in a progression with the rate of accession of comorbid pathology and its severity. The Cardiotrophin-1 level in patients with comorbid pathology is affected by catestatin, leptin, cystatin C, NT-pro BNP, as well as the level of triglycerides, HDL-C, creatinine, and BMI. Cardiotrophin-1 can be considered as a universal biomarker for the development and progression of cardiovascular disorders in patients with comorbid pathology of arterial hypertension, type 2 DM, and obesity.

Serum Cardiotrophin-1 Concentration Is Negatively Associated with Controlled Attenuation Parameters in Subjects with Non-Alcoholic Fatty Liver Disease

Since non-alcoholic fatty liver disease (NAFLD) is highly associated with obesity, cardiovascular disease, and diabetes, biomarkers for the diagnosis of NAFLD have become an important issue. Although cardiotrophin-1 (CT-1) has a protective effect on the liver in NAFLD animal models, the serum levels of CT-1 in human subjects with NAFLD were still unknown. The present study aimed to investigate the relationship between the circulating concentration of CT-1 and the severity of hepatic steatosis graded by the value of the controlled attenuation parameter (CAP) in humans. The study was designed as a cross-sectional study, and a total of 182 subjects were enrolled. Hepatic steatosis measurement was carried out with a Firoscan® device and recorded by CAP. The enrolled study subjects were categorized into CAP < 238 dB/m, 238 ≤ CAP ≤ 259 dB/m, 260 ≤ CAP ≤ 290 dB/m, and CAP > 290 dB/m. Serum CT-1 concentrations were determined by enzyme-linked immunosorbent assay. The association between the serum CT-1 concentration and NAFLD was examined by multivariate linear regression analysis. Body mass index, percentage of body fat, systolic and diastolic blood pressure, alanine aminotransferase (ALT), cholesterol, triglyceride, hemoglobin A1c and homeostatic model assessment for insulin resistance (HOMA-IR) were significantly increased in groups with higher CAP value, whereas high-density lipoprotein cholesterol was significantly decreased. In addition, serum CT-1 concentrations were significantly decreased in subjects with higher CAP values. In multivariate linear regression models, including age, sex, body fat percentage, CAP, high sensitivity- C reactive protein, uric acid, creatinine, ALT, total cholesterol, and HOMA-IR, only age, CAP and uric acid independently associated with CT-1 levels. Moreover, having NAFLD was independently associated with CT-1 after adjustment for sex, obesity and type 2 diabetes. Serum CT-1 concentrations are decreased in subjects with NAFLD and negatively associated with CAP.

Кардіотрофін-1 як можливий маркер ремоделювання міокарда у хворих з есенціальною гіпертензією при носійстві поліморфних варіантів кодувального гена

Мета роботи – поліпшити діагностику ремоделювання лівого шлуночка у хворих з есенціальною гіпертензією (ЕГ) шляхом визначення концентрації кардіотрофіну-1 (КТ-1) у плазмі крові в носіїв поліморфних варіантів гена кардіотрофіну-1 (rs8046707).Матеріали і методи. У дослідження залучено 100 чоловіків віком 40–60 років, мешканців Поділля з ЕГ різної тяжкості. До першої групи увійшли пацієнти з ЕГ II стадії, середній вік – (50,62±0,73) року, до другої групи – пацієнти з ЕГ, ускладненою хронічною серцевою недостатністю (ХСН), середній вік – (51,86±0,81) року. Структурно-функціональні показники міокарда оцінювали за допомогою ультразвукового дослідження серця. Поліморфізм гена КТ-1 (rs8046707) визначали за допомогою методу полімеразної ланцюгової реакції. Концентрацію КТ-1 оцінювали з використанням методу імуноферментного аналізу. Результати та обговорення. Серед чоловіків з ЕГ різної тяжкості статистично значуще частіше реєструються носії генотипів GA+АА – 65,00 % (n=65), ніж генотипу GG – 35,00 % (n=35) (р&lt;0,05). Встановлено, що в носіїв будь-якого поліморфного варіанта гена КТ-1, чоловіків з гіпертрофією лівого шлуночка (ГЛШ) та ХСН на тлі ЕГ найчастіше трапляється концентрична ГЛШ. Водночас рівень КТ-1 у плазмі крові у хворих на ЕГ не тільки є вищим при більшій масі міокарда лівого шлуночка, а й асоційований з носійством певного варіанта кодувального гена. Зокрема, при ЕГ рівні концентрації КТ-1 у плазмі крові при ексцентричній ГЛШ статистично значуще більші в носіїв генотипів GA+АА гена КТ-1 (р&lt;0,05). При ЕГ з ХСН, незалежно від поліморфізму гена КТ-1, концентрація цього пептиду в плазмі крові при різних варіантах ГЛШ вища, ніж у хворих на ЕГ II стадії (р&lt;0,05).Висновки. Таким чином, у чоловіків з ЕГ ІІ стадії та ЕГ з ХСН, носіїв поліморфних варіантів гена КТ-1, статистично значуще частіше траплялася концентрична ГЛШ. Чоловіки з ЕГ ІІ стадії, носії генотипів GA+АА, мають статистично значуще вищий рівень КТ-1 у плазмі крові при концентричній ГЛШ (р&lt;0,05). У разі розвитку ХСН на тлі ЕГ рівень КТ-1 у плазмі крові при носійстві будь-якого варіанта кодувального гена вищий, ніж при ЕГ ІІ стадії.

DO ANDROGENS PREDICT CARDIOVASCULAR RISK INCLUDING CARDIOTROPHIN-1 LEVELS in PATIENTS WITH OBESE and LEAN POLYCYSTIC OVARY SYNDROME.

We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid-IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

Serum levels of cardiotrophin-1 in patients with obstructive hypertrophic cardiomyopathy and in patients with severe left ventricular dysfunction

Relevance. Cardiotrophin-1 (CT-1) is a member of interleukin-6 (IL-6) superfamily and is associated with cardiovascular pathology. The production of CT-1 increases in response to myocardial wall stretching and increase in its rigidity and is also modulated by a wide range of neurohormones and peptides, which allows to monitor CT-1 as a marker of biomechanical stress. However, the prognostic significance of CT-1 in patients with diastolic heart failure with hypertrophic cardiomyopathy (HCM) remains poorly understood.Objective. To study the blood serum cardiotrophin-1 contents and their relationships with NT-proBNP in patients with obstructive hypertrophic cardiomyopathy and in patients with severe left ventricular (LV) dysfunction.Material and Methods. The study comprised a total of 76 patients with obstructive HCM and 31 patients with severe LV dysfunction. The group of patients with HCM comprised patients with obstructive form; the group of patients with severe LV dysfunction included patients with the third type of post-infarction LV remodeling and ejection fraction (EF) of less than 30%. The determination of cardiotrophin-1 and highly sensitive C-reactive protein was carried out by the enzyme immunoassay. The study of NT-proBNP content in blood serum was performed by multiplex immunoassay using the FLEXMAP 3D Luminex Corporation system.Results. The content of cardiotrophin-1 in the blood serum of patients with obstructive HCM was higher than in the group of patients with severe LV dysfunction. The study of NT-proBNP concentrations in the blood serum showed increases in the content in both groups of patients. The median concentrations of NT-proBNP and C-reactive protein in patients with severe LV dysfunction were increased compared to the median concentration in patients with obstructive HCM.Conclusion. The study showed an increase in cardiotrophin-1 content in the blood serum in patients with obstructive HCM with chronic diastolic heart failure. The increase in cardiotrophin-1 content was directly associated with the increase in NTproBNP level in patients with obstructive HCM with chronic diastolic heart failure.

A quantitative detection of Cardiotrophin-1 in chronic heart failure by chemiluminescence immunoassay.

BackgroundCardiotrophin‐1 (CT‐1) is a cytokine that could induce cardiomyocytes hypertrophy and dysfunction. Plasma CT‐1 might serve as a cardiac biomarker both in diagnosis, staging, and prognostic assessment of heart failure.MethodsIn this study, a one‐step paramagnetic particles‐based chemiluminescence immunoassay (MPs‐CILA) for rapid and sensitive detection of plasma CT‐1 was established. Plasma samples were directly incubated with biotin‐labeled anti‐CT‐1 antibody (bio‐Ab) and acridine ester labeled anti‐CT‐1 antibody (AE‐Ab) to form sandwiched complex. The sandwiched CT‐1 was then captured by streptavidin modified paramagnetic particles (MPs‐SA) for rapid separation and signal generation.ResultsThe proposed MPs‐CLIA presents a laudable linear relationship ranging from 7.8 pg/mL to 200 ng/mL with a detection limit of 1.0 pg/mL. The recoveries of spiked human plasma samples at low (10pg/mL), medium (100 pg/mL), and high (800 pg/mL) levels of CT‐1 were 96%, 104%, and 110% respectively. The intra‐analysis coefficient variation (CVs) of the 3 samples was 8.92%, 6.69%, and 3.54%, respectively. And the inter‐analysis coefficient variation (CVs) was 9.25%, 10.9%, and 4.3%, respectively. These results strongly indicate high sensitivity, wide linear range, acceptable precision, and applicable reproducibility of the proposed method to detect plasma level of CT‐1. Finally, Plasma CT‐1 from 140 subjects with or without chronic heart failure was analyzed to assess the clinical application of MPs‐CILA.ConclusionsNoteworthily, the MPs‐CLIA method is highly automated such that it is suitable for high‐throughput detection of CT‐1 in clinical inspection.

Dynamics of left ventricle myocardial deformation, soluble ST2 and cardiotrophin-1 in hypertensive women on combined valsartan/hydrochlorothiazide therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background. The treatment-induced regression of left ventricular hypertrophy (LVH) is associated with improved prognosis in patients with arterial hypertension. However, the assessment of LVH by echo is restricted by substantial measurement variability and low sensitivity to changes during follow-up. The alternative approach could be the dynamic evaluation of myocardial deformation parameters and biochemical markers of cardiac remodeling. The purpose of this study was to assess the dynamics of left ventricle (LV) myocardial deformation, soluble ST2 and cardiotrophin-1 levels in hypertensive women treated with combination of valsartan/hydrochlorothiazide. Methods. The study involved 100 postmenopausal women (mean age – 57.7 ± 4.3 years) with uncomplicated arterial hypertension. All patients were treated with combination of valsartan (80-320 mg; average dose 195 mg) and hydrochlorothiazide (12.5 mg). Ambulatory blood pressure monitoring, conventional and 2-dimensional speckle tracking echocardiography were performed before and 6 months after treatment. The concentrations of cardiotrophin-1 and soluble ST2 were determined by ELISA method. The data are presented as median and interquartile range. Results. Treatment with valsartan/hydrochlorothiazide was effective and well tolerated. Target blood pressure level was achieved in 64 % of the patients. The LV global longitudinal strain (GLS) raised significantly after 6 months of treatment (Table). We found the reduction of mechanical dispersion - parameter, which indirectly reflects myocardial tissue homogenicity. The levels of circulating cardiotrophin-1 and soluble ST2 decreased by 37.93% and 19.74%, respectively (p &amp;lt; 0.0001). Conclusions. The 6-month therapy with valsartan/hydrochlorothiazide was associated with improvement of myocardial deformation parameters with concomitant reduction of soluble ST-2 and cardiotrophin-1 levels. These markers could be more sensitive than standard parameters for hypertensive patients" follow-up. However, this approach should be confirmed in future studies. Parameter Baseline 6-month p Office SBP, mm Hg 148 (140; 157) 135 (124; 143) &amp;lt;0.0001 Office DBP, mm Hg 89 (82; 96) 81 (74; 87) &amp;lt;0.0001 LV GLS, % -19.6 (-18.1; -21.1) -20.4 (-18.9; -21.8) 0.01 Mechanical dispersion, ms 43 (37; 51) 41 (37; 48) 0.04 Cardiotrophin-1, pg/ml 12.2 (9.4; 16.81) 8.5 (6.26; 10.82) &amp;lt;0.0001 Soluble ST2, ng/ml 25.3 (17.93; 29.72) 18.2 (13.93; 25.96) &amp;lt;0.0001 Values are given as median and interquartile range

PROGNOSTIC SIGNIFICANCE OF BLOOD MARKER OF HYPERTROPHY– CARDIOTROPHIN-1 WHEN CARRYING DIFFERENT VARIANTS OF ITS GENE IN MEN WITH ESSENTIAL HYPERTENSION

The aim: To improve diagnosis of essential hypertension with left ventricular hypertrophy and chronic heart failure in men citizens of Podillya region in Ukraine by determining the plasma levels of cardiotrophin-1 in patients with different CT-1 gene variants. Materials and methods: A total of 70 men with no signs of cardiovascular disease and 100 patients with essential hypertension were examined. Among those, 50 participants had hypertension and left ventricular hypertrophy. Other 50 patients had hypertension complicated by chronic heart failure. Results: It was established that in patients with essential hypertension the frequency of the pool of genotypes GA + AA is higher than the genotype GG (p <0.05). Plasma CT-1 levels ≥ 122,895 pg / ml can be used for early diagnosis left ventricular hypertrophy, and the cut-off level is ≥ 303.81 pg / ml (sensitivity 85.7%, specificity 92%) for screening diagnosis of essential hypertension complications in the form of chronic heart failure. Conclusions: In patients with essential hypertension of varying severity, the GA+АА genotypes of CT-1 gene was found to be dominant. They had higher levels of plasma concentration CT-1. The threshold levels of CT-1 for screening diagnosis of essential hypertension with hypertrophy and chronic heart failure in males (who were residents of the Podillya region of Ukraine) were evaluated.

Is cardiotrophin-1 a new risk factor of atrial fibrillation in patients with visceral obesity and metabolic syndrome?

Objective. To determine the concentration of cardiotrophin-1 (CT-1) in patients with metabolic syndrome (MS) and atrial fibrillation (AF) and the relationship with the parameters of obesity and metabolic disorders.Design and methods. In the one-stage case-control study, 352 subjects (35-65 years old) were included: patients with MS (n = 223), among them 107 patients had AF, and two comparison groups consisted of patients with AF without MS (n = 69) and otherwise healthy individuals (n = 60).Results. The serum concentration of CT-1 in patients with AF and MS is higher compared to patients with MS without AF (851,2 (589,1-1146,3) and 590,2 (480,1-922,3) pg/ml, p = 0,005) and healthy subjects (851,2 (589,1-1146,3) and 410,1 (290,2-549,2) pg/ml, p &lt; 0,0001). Patients with AF and MS showed higher serum levels of CT-1 than patients with AF without MS (851,2 (589,1-1146,3) and 681,1 (480,1-823,2) pg/ml, p = 0,004). CT-1 positively correlated with plasma levels of glucose (p = 0,423, p = 0,002) and triglycerides (p = 0,207, p = 0,003), as well as with the waist circumference (p = 0,265, p &lt; 0,001) and the thickness of epicardial fat (p = 0,351, p &lt; 0,001). ROC-analysis demonstrated the increase in serum CT-1 level above 638,1 pg/ml the probability of AF increased by 4 times (odds ratio = 4,0, 95 % confidence interval 2,31-6,94, p &lt; 0,0001).Conclusions. The increase in serum CT-1 concentration is associated with heart remodeling and obesity in patients with MS and probably plays a pathogenetic role in increasing the risk of AF in this cohort of patients.

Endothelial dysfunction in patients with myocardial ischemia or infarction and nonobstructive coronary arteries.

The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are seen more and more often. Endothelial dysfunction (ED) leading to ischemic events has been reported in many of these patients. We aimed to compare patients with MINOCA and INOCA regarding brachial artery flow-mediated endothelium-dependent vasodilation (flow-mediated dilation [FMD]) and plasma concentration of cardiotrophin-1 (CT-1). We included 42 patients with MINOCA and 38 patients with INOCA. Endothelial function was assessed by measuring FMD% and nitroglycerin-mediated dilatation (NMD%) in the brachial artery. The plasma level of CT-1 was determined by solid-phase enzyme-linked immunosorbent assay. FMD% was significantly lower in MINOCA than in INOCA patients (6.45 ± 2.65 vs 8.94 ± 3.32, P < .001), without significant difference in NMD% (10.69 ± 3.19 vs 12.16 ± 3.69, P = .06). Plasma CT-1 levels were not significantly different: 40.1 pg/mL (22.5-102.1) vs 37.2 pg/mL (23.5-67.2), P = .53. Our results suggest worse ED in MINOCA than in INOCA patients, but demonstrated no difference in CT-1 levels between patients with stable and unstable ischemic heart disease and normal coronary arteries.

Carvedilol Diminishes Cardiac Remodeling Induced by High-Fructose/High-Fat Diet in Mice via Enhancing Cardiac β-Arrestin2 Signaling.

Insulin resistance (IR) is a well-known risk factor for cardiovascular complications. This study aimed to investigate the effect of a dietary model of IR in mice on cardiac remodeling, cardiac β-arrestin2 signaling, and the protective effects of carvedilol as a β-arrestin-biased agonist. Insulin resistance was induced by feeding mice high-fructose/high-fat diet (HFrHFD) for 16 weeks. Carvedilol was adiministered for 4 weeks starting at week 13. At the end of the experiment, body weight, heart weight, left and right ventricular thickness, visceral fat weight, fasting blood glucose (FBG), serum insulin, IR index, and serum endothelin-1 were measured. In addition, cardiac tissue samples were histopathologically examined. Also, cardiac levels of cardiotrophin-1, β-arrestin2, phosphatidylinositol 4,5 bisphosphate (PIP2), diacylglycerol (DAG), and phosphoserine 473 Akt (pS473 Akt) were measured. Results showed significant increases in the FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, cardiac fibrosis, and degenerated cardiac myofibrils in HFrHFD-fed mice associated with a significant reduction in cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt. On the other hand, carvedilol significantly reduced the heart weight, FBG, serum insulin, IR index, serum endothelin-1, cardiac DAG, left ventricular thickness, right ventricular fibrosis, and degeneration of cardiac myofibrils. In addition, carvedilol significantly increased cardiac levels of cardiotrophin-1, β-arrestin2, PIP2, and pS473 Akt. Carvedilol enhances cardiac β-arrestin2 signaling and reduces cardiac remodeling in HFrHFD-fed mice.

Functional Improvement of Human Cardiotrophin 1 Produced in Tobacco Chloroplasts by Co-Expression with Plastid Thioredoxin m

Human cardiotrophin 1 (CT1), a cytokine with excellent therapeutic potential, was previously expressed in tobacco chloroplasts. However, the growth conditions required to reach the highest expression levels resulted in an impairment of its bioactivity. In the present study, we have examined new strategies to modulate the expression of this recombinant protein in chloroplasts so as to enhance its production and bioactivity. In particular, we assessed the effect of both the fusion and co-expression of Trx m with CT1 on the production of a functional CT1 by using plastid transformation. Our data revealed that the Trx m fusion strategy was useful to increase the expression levels of CT1 inside the chloroplasts, although CT1 bioactivity was significantly impaired, and this was likely due to steric hindrance between both proteins. By contrast, the expression of functional CT1 was increased when co-expressed with Trx m, because we demonstrated that recombinant CT1 was functionally active during an in vitro signaling assay. While Trx m/CT1 co-expression did not increase the amount of CT1 in young leaves, our results revealed an increase in CT1 protein stability as the leaves aged in this genotype, which also improved the recombinant protein’s overall production. This strategy might be useful to produce other functional biopharmaceuticals in chloroplasts.

Effects of Pterostilbene on Diabetes, Liver Steatosis and Serum Lipids.

Pterostilbene, a phenolic compound derived from resveratrol, possesses greater bioavailability than its parent compound due to the presence of two methoxyl groups. In this review, the beneficial effects of pterostilbene on diabetes, liver steatosis and dyslipidemia are summarized. Pterostilbene is a useful bioactive compound in preventing type 1 diabetes, insulin resistance and type 2 diabetes in animal models. Concerning type 1 diabetes, the main mechanisms described to justify the positive effects of this phenolic compound are increased liver glycogen content and hepatic glucokinase and phosphofructokinase activities, the recovery of pancreatic islet architecture, cytoprotection and a decrease in serum and pancreatic pro-inflammatory cytokines. As for type 2 diabetes, increased liver glucokinase and glucose-6-phosphatase and decreased fructose-1,6-biphosphatase activities are reported. When insulin resistance is induced by diets, a greater activation of insulin signaling cascade has been reported, increased cardiotrophin-1 levels and liver glucokinase and glucose- 6-phosphatase activities, and a decreased fructose-1,6-biphosphatase activity. Data concerning pterostilbene and liver steatosis are scarce so far, but the reduction in oxidative stress induced by pterostilbene may be involved since oxidative stress is related to the progression of steatosis to steatohepatitis. Finally, pterostilbene effectively reduces total cholesterol, LDL-cholesterol and serum triglyceride levels, while increases HDL-cholesterol in animal models of dyslipidemia.

The Expression of Adipose Tissue-Derived Cardiotrophin-1 in Humans with Obesity.

Cardiotrophin-1 (CT-1) is a gp130 cytokine that was previously characterized for its effects on cardiomyocytes and identified as a marker of heart failure. More recent studies reported elevated circulating levels of CT-1 in humans with obesity and metabolic syndrome (MetS). However, a subsequent rodent study implicated CT-1 as a potential therapeutic target for obesity and MetS. Adipose tissue (AT) is broadly acknowledged as an endocrine organ and is a substantial source of CT-1. However, no study has examined the expression of adipose-derived CT-1 in humans. We present the first analysis of CT-1 mRNA expression in subcutaneous AT and its association with clinical variables in 22 women with obesity and 15 men who were 40% overfed for 8-weeks. We observed that CT-1 expression was higher in the subcutaneous abdominal (scABD) than the femoral (scFEM) depot. Importantly, we reveal that scFEM but not scABD, CT-1 expression was negatively associated with visceral adiposity and intrahepatic lipid, while positively correlated with insulin sensitivity in obese women. Also, men with higher CT-1 levels at baseline had less of a decline in insulin sensitivity in response to overfeeding. Our data provide new knowledge on the regulation of adipose-derived CT-1 in obesity and during weight gain in response to overfeeding in humans and suggest that CT-1 may play a protective role in obesity and related disorders.

FRI-288-Physiological levels of cardiotrophin-1 (CT-1) contribute to fasting-induced free fatty acid mobilization

FRI-288-Physiological levels of cardiotrophin-1 (CT-1) contribute to fasting-induced free fatty acid mobilization

Effects of chronic REM sleep deprivation on lipocalin-2, nitric oxide synthase-3, interleukin-6 and cardiotrophin-1 levels: an experimental rat model

The purpose of this study was to investigate the effects of chronic rapid eye movement sleep deprivation on cardiovascular system using blood levels of lipocalin-2, nitric oxide synthase-3, interleukin-6, and cardiotrophin-1. We included sixteen Wistar Albino rats of 300–350 g weight in the study. To create a chronic rapid eye movement sleep deprivation, we used water tanks with platform including modified multiple sleep deprivation platforms, and we used water tanks with grid to grab for control group. We left 8 rats in water tanks with platform (study group) and 8 rats in water tanks with grid to grab (control group) for 21 days. Finally, we drew blood from the hearts of the rats, just before scarifying all the rats. We performed statistical comparisons of lipocalin-2, nitric oxide synthase-3, interleukin-6 and cardiotrophin-1 levels between the study group and the control group. The lipocalin-2, nitric oxide synthase-3, interleukin-6 and cardiotrophin-1 levels were 29.8 ng/mL, 116.99 ng/mL, 4.32 ng/L and 33.26 ng/L in the study group, respectively; and 122.74 ng/mL, 85.74 ng/mL, 3.23 ng/L and 23.02 ng/L in the control group, respectively. In the study group, mean lipocalin-2 levels were significantly lower (p = 0.003) but mean cardiotrophin-1 levels were significantly higher compared with the control group (p = 0.001). Mean interleukin-6 and nitric oxide synthase-3 levels did not significantly differ between the groups (p = 0.135 and p = 0.157). Our study showed that chronic rapid eye movement sleep deprivation might be associated with cardiovascular diseases owing to higher blood cardiotropin-1 levels in the study group, a novel biomarker that has been shown to indicate endothelial dysfunction, atherosclerosis and fibrosis in the cardiovascular system.

CT-1 (Cardiotrophin-1)-Gal-3 (Galectin-3) Axis in Cardiac Fibrosis and Inflammation.

Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 µg/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1-treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF.

Effect of Salt Intake on the Serum Cardiotrophin-1 Levels in Chinese Adults

Background: Dietary sodium affects fluctuations in blood pressure (BP) and vascular function. Cardiotrophin-1 (CT-1), a stress-induced cytokine that belongs to the interleukin 6 family, is released by cells in response to potentially harmful stresses and plays a pivotal role in congestive heart failure, hypertension and arterial stiffness. In this study, we performed a randomized trial to confirm the effects of altered salt intake on the serum CT-1 levels in humans. Methods: Forty-four subjects (18–65 years of age) were selected from a rural community in northern China. All subjects initially maintained a baseline period for 3 days, transitioned to a low-salt (LS) diet for 7 days (3.0 g/day of NaCl) and then a high-salt (HS) diet for an additional 7 days (18.0 g/day of NaCl). Results: For the whole group, the serum CT-1 concentrations were significantly increased in the HS period compared to those of the LS period (293.50 ± 137.70 vs. 360.40 ± 162.83 pg/mL, p = 0.040). The serum CT-1 concentrations significantly decreased from the baseline period to the LS diet (419.91 ± 123.50 to 256.49 ± 109.75 pg/mL, p < 0.01) and significantly increased from the LS to HS diet (256.49 ± 109.75 to 414.39 ± 191.21 pg/mL, p < 0.01). These changes were observed in salt-sensitive (SS) individuals but not in salt-resistant (SR) individuals. In addition, a significant positive relationship was observed between the changes in the CT-1 concentrations and systolic BP as well as the changes in the mean arterial pressure from the LS period to the HS period (r = 0.376, p = 0.012; r = 0.311, p = 0.040). The serum CT-1 concentrations were positively correlated with the 24-h urinary sodium-to-potassium (Na/K) excretion ratios during both of the LS and HS diet intervention periods in SS subjects (r = 0.621, p < 0.01), but this correlation was not evident in SR subjects (r = 0.208, p = 0.107). Conclusions: Our study indicates that variations in dietary salt intake affect the serum CT-1 levels in Chinese adults.

P653Cardiac remodeling in highly trained athletes is associated with rho kinase activation and increased levels of cardiotrophin-1

P653Cardiac remodeling in highly trained athletes is associated with rho kinase activation and increased levels of cardiotrophin-1