Dataset Information

S-Thiolation Targets Albumin in Heart Failure.

ABSTRACT: Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO2/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H2O2, we showed a significant decrease of cell viability in cells treated with thio-HSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression.

SUBMITTER: Brioschi M

PROVIDER: S-EPMC7463808 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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S-Thiolation Targets Albumin in Heart Failure.

Brioschi Maura M Gianazza Erica E Mallia Alice A Zoanni Beatrice B Altomare Alessandra A Martinez Fernandez Alma A Agostoni Piergiuseppe P Aldini Giancarlo G Banfi Cristina C

Antioxidants (Basel, Switzerland) 20200817 8

Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease ...[more]

PMID: 32824562

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Project description: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.

Project description:BackgroundHeart failure is frequently associated with hypoalbuminaemia and poor prognosis. Acute heart failure (AHF) patients are commonly treated with intravenous albumin to improve osmotic pressure and haemodynamics. However, the effects of exogenous albumin supplementation on the fatality rate of AHF patients have not yet been demonstrated. Therefore, the present study strived to examine the impacts of albumin injections on the mortality rate of patients with AHF.MethodsThis retrospective cohort study evaluated the clinical outcomes of all consecutive hospitalized patients. Data were collected from medical records. The primary end-point was a composite of intubation, emergency renal replacement, or mortality in a time-to-event analysis. An inverse probability-weighted multivariable Cox model was used to compare outcomes between patients who were treated with albumin and those who were not based on the propensity score.ResultsAmong the 1420 consecutive patients hospitalized in our hospital with acute decompensated heart failure between 1 January 2017 and 27 February 2021, 382 were excluded, 337 (32.5%) were administered albumin (median treatment dose of 29.0 g), and 701 (67.5%) were not. The albumin exposure varied by body mass index, age group, previous diagnoses, clinical signs and symptoms, laboratory tests, and use of other drugs in the unmatched sample. The patients receiving albumin exhibited a lower serum albumin level at baseline in contrast with those who were not treated with albumin (median, 37.3 g/L vs. 31.7 g/L, respectively). Overall, primary end-point events occurred in 357 patients (34.4%) (79 died without being intubated or during an emergency renal replacement therapy, 118 were intubated and 160 had an emergency renal replacement therapy). In the inverse probability weighted multivariable analysis based on the propensity score, albumin use was not significantly associated with the composite primary end-point (hazard ratio, 1.05; 95% confidence interval, 0.75-1.47).ConclusionIn this observational study of AHF patients hospitalized in our hospital, the administration of albumin did not show a relationship with either a greatly reduced or aggregated risk of the composite end-point of intubation, emergency renal replacement therapy, or death. Therefore, randomized controlled trials of albumin administration are needed for patients with AHF.

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S-Thiolation Targets Albumin in Heart Failure.

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S-Thiolation Targets Albumin in Heart Failure.

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