N-Terminal Pro–Atrial Natriuretic Peptide Measurement in Plasma Suggests Covalent Modification

Hunter, Ingrid; Alehagen, Urban; Dahlström, Ulf; Rehfeld, Jens F.; Crimmins, Dan L.; Goetze, Jens P.

doi:10.1373/clinchem.2011.166330

Cited by 45 publications

(35 citation statements)

References 14 publications

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“…Plasma proANP was measured with an in-house assay, a so-called processing-independent assay (2 ). Assay performance and its correlation to midregional proANP measurement have previously been published (3 ).…”

Section: To the Editormentioning

confidence: 99%

Plasma proANP Decreases after Meal Intake

Goetze

2013

Clinical Chemistry

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Section: To the Editormentioning

confidence: 99%

Plasma proANP Decreases after Meal Intake

Goetze

2013

Clinical Chemistry

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“…Among protein and peptide hormones there are several examples of incomplete amino acid derivatization. For instance, only half of the gastrin peptides in tissue and blood are O-sulfated [5,10]; less than half of tissue and circulating ghrelin pep tides are octanoylated [23][24][25]; only a fraction of the circulating proBNP-and proANP-derived peptides are glycosylated [26][27][28]; and likewise only a minor fraction of growth hormone and chaperonin-10 are N-terminally acetylated [29]; whereas two bioactive products of proopiomelanocortin (POMC), a-MSH and P-endorphin, are more extensively, but not com pletely N-acetylated [30,31]. On this background the dogma that bioactive endogenous CCK peptides are always completely sulfated was a challenge that required examination.…”

Section: Discussionmentioning

confidence: 99%

Measurement of nonsulfated cholecystokinins

Agersnap

Rehfeld

2014

Scandinavian Journal of Clinical and Laboratory Investigation

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Most proteins undergo posttranslational modifications that govern the function of the protein. In synchrony, correspondingly unmodified proteins that are functionally silent or act differently may also be synthesized. The gut hormone precursor, procholecystokinin (proCCK) is an example of a protein that is heavily modified. An essential modification is O-sulfation of Y₇₇, which is necessary for the gallbladder emptying effect of CCK peptides via the CCKA-receptor. In order to examine possible in vivo synthesis also of nonsulfated CCK, we have established a two-step analysis that requires tryptic cleavage at a defined processing site in proCCK (R₇₅-D₇₆) followed by monospecific RIA-measurement of the then exposed nonsulfated N-terminal sequence of CCK-8 (DYMGW…). The analysis shows that endocrine cells in the gut synthesize nonsulfated CCK peptides (-58, -33, -22, and -8) in the order of 20-35% of the corresponding sulfated CCKs. Since nonsulfated CCK peptides are full agonists of the CCKB-receptor, the assay has revealed a hitherto unrecognized gut hormonal peptide system. The assay may prove useful in the diagnosis and control of diseases with hyperCCKemia. This includes CCK-producing neuroendocrine tumors such as the recently described CCKomas and medullary thyroid C-cell carcinomas.

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“…The method has been validated previously (16,25). Pro-B-type natriuretic peptide was measured on a Modular E platform (Roche, Jena, Switzerland); this assay has been used for more than a decade as the "gold standard" in biochemical assessment of heart failure patients.…”

Section: Study Populationmentioning

confidence: 99%

Cardiac sympathetic imaging withmIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function

Möller¹,

Mortensen

Bendtsen

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Madsen JL. Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function. Am J Physiol Gastrointest Liver Physiol 303: G1228 -G1235, 2012. First published September 27, 2012 doi:10.1152/ajpgi.00303.2012.-Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified 123 I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in patients with cardiac failure it predicts outcome. In this study, we aimed to investigate cardiac sympathetic neuronal function in cirrhosis by mIBG scintigraphy in relation to cardiovascular function. Ten patients with alcoholic cirrhosis and 10 age-and sexmatched healthy controls participated in the study. Heart/mediastinum (H/M) ratios of mIBG uptake were calculated 15 and 230 min after intravenous injection of mIBG. Furthermore, washout rate (WOR) of mIBG was calculated. The patients underwent a liver vein catheterization with determination of splanchnic and systemic hemodynamics and measurement of HRV and BRS. mIBG-scintigraphy revealed significantly increased WOR in patients with cirrhosis compared with controls (P Ͻ 0.005), whereas H/M uptakes were equal in the groups. Forty percent of the patients had reduced uptake of mIBG in the infero-lateral segment of the left ventricle. WOR correlated significantly with central circulation time, an estimate of central hypovolemia (r ϭ Ϫ0.64, P Ͻ 0.05) and frequency-corrected QTF interval (r ϭ 0.71, P ϭ 0.01). Patients with cirrhosis had significantly decreased HRV and BRS correlating with indicators of abnormal cathecholamine uptake by mIBG although the catecholamine level was normal in the patients. In conclusion, in alcoholic cirrhosis, mIBG scintigraphy reveals autonomic dysfunction and impaired myocardial distribution of sympathetic nervous activity. It is associated to indicators of central hypovolemia, QT interval, and decreased HRV and BRS. Measurement of myocardial catecholamine uptake by mIBG may add important information on autonomic and cardiac dysfunction in cirrhosis. liver failure; autonomic dysfunction; single-photon emission computerized tomography; cirrhotic cardiomyopathy; baroreflex sensitivity; sympathetic nervous system; heart rate variability; chronic liver disease; hyperdynamic circulation; cirrhotic cardiomyopathy; autonomic dysfunction; 123 I-metaiodobenzylguanidine AUTONOMIC AND CARDIAC DYSFUNCTION is frequent in cirrhosis and includes impaired baroreflex sensitivity (BRS) and heart rate variability (HRV) in the setting of increased activity of the sympathetic nervous system (SNS) (10, 33, 41). The recently described, cirrhotic cardiomyopathy is seen in more than 50% of the patients and includes diastolic and systolic dysfunction as well as prolonged 43). Cirrhotic cardiomyopathy may contribute to development of complications such as renal failure and reduced survival (35). SNS is often activated...

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N-Terminal Pro–Atrial Natriuretic Peptide Measurement in Plasma Suggests Covalent Modification

Cited by 45 publications

References 14 publications

Plasma proANP Decreases after Meal Intake

Plasma proANP Decreases after Meal Intake

Measurement of nonsulfated cholecystokinins

Cardiac sympathetic imaging withmIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function

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