Non-competitive immunochemiluminometric assay for cardiotrophin-1 detects elevated plasma levels in human heart failure

2002 ◽  
Vol 102 (4) ◽  
pp. 411-416 ◽  
Author(s):  
Leong L. NG ◽  
Russell J. O'BRIEN ◽  
Bettina DEMME ◽  
Sonja JENNINGS
Keyword(s):  
Heart Failure ◽  
Amino Acids ◽  
Plasma Levels ◽  
Limit Of Detection ◽  
Linear Increase ◽  
Full Length ◽  
Human Heart Failure ◽  
Competitive Assay ◽  
Coefficients Of Variation ◽  
Patients With Heart Failure

Cardiotrophin-1 (CT-1) leads to a specific form of ventricular hypertrophy characterized by sarcomeres added in series, and has been reported to be elevated in heart failure. Previous competitive assays for CT-1 necessitate the extraction of plasma and involve prolonged incubations. We describe the development of a non-competitive assay for CT-1 that can measure plasma levels without the need for extraction. Two antibodies specific for the mid-section (amino acids 105-120) and C-terminal (amino acids 186-199) portions of CT-1 were developed in rabbits. One antibody was immobilized and used as the capture antibody. The other antibody was affinity purified and biotinylated. Unextracted plasma was incubated with these antibodies, and detection was with methylacridinium ester-labelled streptavidin. Plasma was obtained from 40 patients with heart failure and 40 normal control subjects. The non-competitive assay demonstrated a linear increase in chemiluminescence (measured as relative light units) with increasing amounts of full-length recombinant CT-1, with no evidence of a hook effect at high concentrations. The lower limit of detection was 2.9 fmol/ml. Intra-assay coefficients of variation ranged from 3.1% to 4.2% in the 10-40fmol/well concentration range, and interassay coefficients of variation ranged from 3.5% to 4.5% in the 550-950fmol/ml range. Measurements of CT-1 levels in patients with heart failure (median 166.5fmol/ml; range 49.5-2788fmol/ml) revealed very significantly elevated levels compared with those in normal controls (median 43.5fmol/ml; range 11.2-258.6fmol/ml; P < 0.0001 by Mann-Whitney test). At a CT-1 concentration of 68fmol/ml, sensitivity and specificity were 95% and 82.5% respectively. Thus this new non-competitive immunochemiluminometric assay for CT-1 could successfully detect full-length recombinant CT-1 in unextracted plasma, and demonstrated that plasma levels of CT-1 were significantly elevated in patients with heart failure.

The renal and cardiovascular effects of natriuretic peptides

2017 ◽  
Vol 41 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Philip Ching Yat Wong ◽  
Jun Guo ◽  
Aidong Zhang
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Levels ◽  
Cardiovascular Effects ◽  
Target Cells ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Endocrine Organs ◽  
Patients With Heart Failure

The landmark report by de Bold et al. in 1981 signified the heart as one of the endocrine organs involved in fluid and salt balance (de Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. Life Sci 28: 89–94, 1981). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are secreted from cardiomyocytes in response to cardiac stretch as in the case of heart failure, whereas C-type natriuretic peptide (CNP) is secreted from endothelial and renal cells in response to cytokines and endothelium-dependent agonists, such as acetylcholine. Binding ANP or BNP to natriuretic peptide receptor A induces cyclic guanylyl monophosphate as second messenger in the target cells to mediate the following: natriuresis; water diuresis; increasing glomerular filtration rate; decreasing systemic sympathetic activities; plasma volume; cardiac output and blood pressure; and curbing mitoses of heart fibroblasts and hypertrophy of cardiovascular muscle cells. ANP, BNP, and CNP are cleared from the bloodstream by natriuretic peptide receptor C and degraded by an ectoenzyme called neprilysin (NEP). The plasma levels of BNP are typically >100 pg/ml in patients with congestive heart failure. Sacubitril/valsartan is an angiotensin receptor NEP inhibitor that prevents the clinical progression of surviving patients with heart failure more effectively than enalapril, an angiotensin-converting enzyme inhibitor. A thorough understanding of the renal and cardiovascular effects of natriuretic peptides is of major importance for first-year medical students to gain insight into the significance of plasma levels of BNP in patients with heart failure.

scholarly journals The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure

2019 ◽  
Vol 109 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Bernadet T. Santema ◽  
Michelle M. Y. Chan ◽  
Jasper Tromp ◽  
Martin Dokter ◽  
Haye H. van der Wal ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Plasma Levels ◽  
Validation Cohort ◽  
Post Hoc Analysis ◽  
Patients With Heart Failure ◽  
History Of ◽  
Post Hoc ◽  
Multivariable Adjustment

Abstract Background In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). Methods In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). Results Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th–75th percentile 1897–6486] versus 1788 [682–3870], adjusted p < 0.001, versus 2231 pg/mL [902–5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062–5253] versus 2545 [1686–4337], adjusted p = 0.36, versus 2294 [1471–3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. Conclusion These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF. Graphic abstract

scholarly journals Prognostic Impact of Plasma Levels of Cyclophilin a in Patients with Heart Failure

2016 ◽  
Vol 22 (9) ◽  
pp. S179 ◽  
Author(s):  
Tomohiro Ohtsuki ◽  
Kimio Satoh ◽  
Junichi Omura ◽  
Nobuhiro Kikuchi ◽  
Taijyu Sato ◽  
...  
Keyword(s):  
Heart Failure ◽  
Plasma Levels ◽  
Cyclophilin A ◽  
Prognostic Impact ◽  
Patients With Heart Failure

scholarly journals Raised homocystein plasma concentration in patients with Heart Failure: clinical significance

2016 ◽  
Vol 68 (2) ◽  
Author(s):  
E. Vizzardi ◽  
S. Nodari ◽  
C. Fiorina ◽  
M. Metra ◽  
L. Dei Cas
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Vascular Disease ◽  
Plasma Levels ◽  
Nyha Class ◽  
Plasma Homocysteine ◽  
Functional Class ◽  
Nyha Functional Class ◽  
Control Subjects ◽  
Patients With Heart Failure

Elevated plasma levels of homocysteine is associated with increased risk of thrombotic and atherosclerotic vascular disease. Several studies have demonstrated that hyperhomocysteinemia is an indipendent risk factor for vascular disease and is associated to heart failure. However there are no data regarding the association between homocysteine and various objective as well as subjective measures of heart failure. We hypothesized that plasma homocysteine is associated with clinical and echocardiographic signs of heart failure. On this ground we have analysed levels of homocysteine in patients with heart failure and possible correlation between these levels and clinical-functional pattern (NYHA class and ejection fraction). Methods: Plasma homocysteine levels were determined in 123 patients with dilated cardiomyopathy (59 males, 64 females, mean age 67±10 years, mean EF 31±11% and mean NYHA 2.4±0.9, 47 idiopatic and 76 postischemic cardiomyopathy) and 85 healthy control subjects (homogeneus group for sex and age). Patients with chronic renal failure, vitamin B12 and folate deficiency or factors affecting homocysteine plasma levels were escluded from this study. Homocysteine levels were determined in coded plasma samples by immunoenzimatic methods. Results: Patients with heart failure had a higher homocysteine level (mcg/L) than control subjects (21.72±10.28 vs 12.9±6.86, p&lt;0,001) both postischemic (20.89±9.6 vs 12.9±6.86, p&lt;0,001) and idiopatic cardiomiopathy (23.0±11.2 vs 12.9±6.86, p&lt;0,001). A significant correlation was observed between homocysteine and NYHA functional class (p&lt;0,001), age (p&lt;0,001), creatinine (p&lt;0,001), colesterol (p&lt;0,05) while no correlations were observed with hemodynamic (HR, BP), functional (ejection fraction) and other metabolic parameters (triglycerides). Serum homocysteine was lowest in control and increased with increasing NYHA class. In idiopatic cardiomiopathy the correlation between homocysteine and NYHA functional class, creatinine (p&lt;0,001), fibrinogen (p&lt;0,05) was confirmed; in postischemic cardiomiopathy a significant correlation with creatinine and NYHA class (p&lt;0,001) and with triglycerides (p&lt;0,05) was also found. Conclusion: Plasma homocysteine was directly related to NYHA class. This observation may underline the strong relations of plasma homocysteine to congestive heart failure. Further research is indicated to evaluate a causal or noncausal mechanism for this association.

scholarly journals Serum and Urine Albumin and Response to Loop Diuretics in Heart Failure

2019 ◽  
Vol 14 (5) ◽  
pp. 712-718 ◽  
Author(s):  
Antonios Charokopos ◽  
Matthew Griffin ◽  
Veena S. Rao ◽  
Lesley Inker ◽  
Krishna Sury ◽  
...  
Keyword(s):  
Heart Failure ◽  
Serum Albumin ◽  
Transitional Care ◽  
Care Center ◽  
Loop Diuretics ◽  
Human Heart Failure ◽  
Diuretic Resistance ◽  
Urine Albumin ◽  
Patients With Heart Failure ◽  
Diuretic Efficiency

Background and objectivesDiuretic resistance can limit successful decongestion of patients with heart failure. Because loop diuretics tightly bind albumin, low serum albumin and high urine albumin can theoretically limit diuretic delivery to the site of action. However, it is unknown if this represents a clinically relevant mechanism of diuretic resistance in human heart failure.Design, setting, participants, & measurementsIn total, 208 outpatients with heart failure at the Yale Transitional Care Center undergoing diuretic treatment were studied. Blood and urine chemistries were collected at baseline and 1.5 hours postdiuretic administration. Urine diuretic levels were normalized to urine creatinine and adjusted for diuretic dose administered, and diuretic efficiency was calculated as sodium output per doubling of the loop diuretic dose. Findings were validated in an inpatient heart failure cohort (n=60).ResultsSerum albumin levels in the outpatient cohort ranged from 2.4 to 4.9 g/dl, with a median of 3.7 g/dl (interquartile range, 3.5–4.1). Serum albumin had no association with urinary diuretic delivery (r=−0.05; P=0.52), but higher levels weakly correlated with better diuretic efficiency (r=0.17; P=0.02). However, serum albumin inversely correlated with systemic inflammation as assessed by plasma IL-6 (r=−0.35; P<0.001), and controlling for IL-6 eliminated the diuretic efficiency-serum albumin association (r=0.12; P=0.12). In the inpatient cohort, there was no association between serum albumin and urinary diuretic excretion (r=0.15; P=0.32) or diuretic efficiency (r=−0.16; P=0.25). In the outpatient cohort, 39% of patients had microalbuminuria, and 18% had macroalbuminuria. There was no correlation between albuminuria and diuretic efficiency after adjusting for kidney function (r=−0.02; P=0.89). Results were similar in the inpatient cohort.ConclusionsSerum albumin levels were not associated with urinary diuretic excretion, and urinary albumin levels were not associated with diuretic efficiency.

Non-competitive immunochemiluminometric assay for cardiotrophin-1 detects elevated plasma levels in human heart failure

2002 ◽  
Vol 102 (4) ◽  
pp. 411 ◽  
Author(s):  
Leong L. NG ◽  
Russell J. O’BRIEN ◽  
Bettina DEMME ◽  
Sonja JENNINGS
Keyword(s):  
Heart Failure ◽  
Plasma Levels ◽  
Human Heart ◽  
Elevated Plasma ◽  
Human Heart Failure

Significance of Branched-Chain Amino Acids in Lean Patients With Heart Failure

2016 ◽  
Vol 22 (9) ◽  
pp. S218 ◽  
Author(s):  
Takayuki Namba ◽  
Toyokazu Kimura ◽  
Shunpei Horii ◽  
Risako Yasuda ◽  
Takumi Toya ◽  
...  
Keyword(s):  
Heart Failure ◽  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Patients With Heart Failure ◽  
Branched Chain

Significance of Low Plasma Levels of Brain-Derived Neurotrophic Factor in Patients With Heart Failure

2015 ◽  
Vol 116 (2) ◽  
pp. 243-249 ◽  
Author(s):  
Seiji Takashio ◽  
Seigo Sugiyama ◽  
Megumi Yamamuro ◽  
Hiroyuki Takahama ◽  
Tomohiro Hayashi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Neurotrophic Factor ◽  
Plasma Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Patients With Heart Failure

Abstract 282: Phospholamban Truncation Mutations Including Heart Failure Mutant L39stop Disrupt Membrane Localization.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Neha Abrol ◽  
Nikolai Smolin ◽  
Chris Stefonowicz ◽  
Seth L Robia
Keyword(s):  
Heart Failure ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Full Length ◽  
Membrane Localization ◽  
Minimum Length ◽  
Human Heart Failure ◽  
C Terminus ◽  
Dynamics Simulations ◽  
And Function

Introduction: Phospholamban (PLB) is an integral sarcoplasmic reticulum (SR) membrane protein, which directly regulates cardiac Ca 2+ handling and contractility by reversibly inhibiting SR Ca 2+ ATPase (SERCA). Our previous studies have suggested that the naturally occurring human heart failure mutation of PLB, L39X disrupts membrane localization. Hypothesis: We hypothesize that the membrane localization of PLB is a prerequisite for PLB oligomerization and interaction with SERCA. The truncation mutations in C-terminus of PLB will disrupt membrane localization, PLB oligomerization, and SERCA regulation. Results and Methods: To identify the minimum length of PLB required for membrane localization and function, we generated a series of C-terminal transmembrane truncation mutants of PLB (tagged N-terminally with Cer or YFP) including L51X, M50X, V49X, I48X, I38X, I33X, and the heart-failure mutant L39X. Confocal microscopy revealed that progressive truncation of the C-terminal residues of PLB resulted in escalating increase in mislocalization of PLB to the cytoplasm and nucleus. In addition, we observed an increased solubilization of PLB as indicated by loss of YFP fluorescence after selective permeabilization of the plasma membrane by saponin. As expected, there was no change in localization of Cer-SERCA upon saponin permeabilization. Next, western blot analysis exhibited a decrease in molecular weight corresponding to the relative sizes of truncation mutants compared to full length PLB, indicating that protein degradation is not the cause of membrane mislocalization. Fluorescence resonance energy transfer analysis revealed that truncating the C-terminal residues of PLB results in a progressive decrease in apparent affinity of PLB oligomerization and interaction with SERCA. Finally, molecular dynamics simulations exhibited that the heart failure mutant L39X was unstable compared to full length PLB pentamer and started protruding out of the bilayer until complete solubilization. Conclusions: Truncating only two C-terminal residues of PLB resulted in significant mislocalization, while deleting five or more residues profoundly disrupted membrane localization, PLB oligomerization and SERCA regulation.

Sign in / Sign up

Export Citation Format

Share Document