Impact of Age, Phenotype and Cardio-Renal Function on Plasma C-Type and B-Type Natriuretic Peptide Forms in an Adult Population.
Department of Medicine, University of Otago, Christchurch, New Zealand. Clinical Endocrinology
(Impact Factor: 3.46).
09/2012; 78(5). DOI: 10.1111/cen.12035
In contrast to the cardiac hormones, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), variations in plasma concentrations of C-type natriuretic peptide (CNP) in healthy adults are ill-defined, limiting their clinical application.
Our objective was to define the effect of age, phenotype (gender, height, BMI), and cardiac and renal function on plasma CNPs in an adults population without renal or cardiovascular disease.
This was a prospective cross-sectional observational study of adult volunteers, aged 21–80 years, randomly selected from the electoral roll.
Plasma CNP and its associated aminoterminal propeptide (NTproCNP) were measured in 258 subjects and related to age, gender, height and plasma creatinine. Subgroup analyses seeking associations with cardiac function (plasma BNP and NTproBNP) and bone turnover bone-specific alkaline phosphatase (bALP) were also determined.
Plasma concentrations of CNPs in men continued to decline from adolescent values to reach a nadir in the 5th decade after which values increased. Similar but less marked changes occurred in women. In both sexes, NTproCNP was inversely and independently correlated with height. In contrast to B-type natriuretic peptides (BNPs), NTproCNP was higher in men, significantly related to creatinine and positively related to bALP.
Gender- and age-specific changes affect CNPs in adults. Inverse associations of NTproCNP with adult height, positive correlation with creatinine – and in contrast to CNP – no association with BNP are further unique findings distinguishing NTproCNP, which need to be considered in future studies.
Available from: Eric A Espiner
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C-type natriuretic peptide (CNP) is a paracrine growth factor critical in endochondral bone growth. Amino-terminal CNP (NTproCNP), measurable in plasma, correlates with growth-plate activity and can be used as a biomarker of growth velocity in children. Because severe inflammation in adults increases CNP, we studied CNP peptides and inflammatory markers in children with acute illness.
Forty-two children aged 2 mo to 5 y with acute illness warranting admission to an acute assessment unit were studied. Fifteen age-matched healthy children attending an outpatient clinic served as controls. Venous CNP concentrations were measured at admission, along with markers of acute inflammation (body temperature, C-reactive protein (CRP), and white blood cell count) in children with acute illness.
NTproCNP and CNP SD scores (SDSs) in the acutely ill group were significantly suppressed (P < 0.001) as compared with those of healthy children or healthy population norms. NTproCNP SDS was significantly inversely related to body temperature (r = -0.42, P < 0.01) and CRP (r = -0.56, P < 0.001).
Acute inflammation in young children potently reduces CNP production, which needs to be considered when screening for growth disorders. Our data raise the possibility that the adverse effects of inflammatory cytokines on skeletal growth may be mediated in part by reduced CNP.
Available from: Bang-Gee Hsu
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ABSTRACT: Atrial natriuretic peptide (ANP) is a potent lipolytic agent that acts in adipose tissue. Low levels of ANP might lead to reduced lipolysis and excessive weight gain, which could be one of the biological alterations that contribute to the development of obesity. The aim of the present study was to evaluate the relationship between metabolic syndrome and fasting serum ANP concentrations in older adults.
Fasting blood samples were obtained from 90 older adults. Metabolic syndrome and its components were defined using diagnostic criteria from the International Diabetes Federation.
A total of 40 older adults (44.4%) had metabolic syndrome. Fasting ANP level was negatively correlated with metabolic syndrome (P = 0.015). Univariate linear regression analysis showed that high-density lipoprotein cholesterol (P < 0.001) was positively correlated with serum logANP levels, whereas waist circumference (P = 0.001) and body fat mass (P = 0.002) were negatively correlated with fasting serum logANP levels. Multivariate forward stepwise linear regression analysis of the significant variables showed that high-density lipoprotein cholesterol (β = 0.419, R(2) = 0.268, P < 0.001) and body fat mass (β = -0.396, R(2) = 0.154, P = 0.002) were independent predictors of fasting serum logANP levels in geriatric persons.
Serum ANP levels were reduced in geriatric persons affected by metabolic syndrome. Body fat mass and high-density lipoprotein cholesterol were independent predictors of fasting serum ANP levels in older adults. Geriatr Gerontol Int 2013; ●●: ●●-●●.
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ABSTRACT: BackgroundC-type natriuretic peptide (CNP)/natriuretic peptide receptor 2 (NPR2) signalling is essential for long bone growth. Enhanced CNP production caused by chromosomal translocations results in tall stature, a Marfanoid phenotype and skeletal abnormalities. A similar phenotype was described in a family with an activating NPR2 mutation within the guanylyl cyclase domain.CaseHere we describe an extremely tall male without skeletal deformities, with a novel NPR2 mutation (p.Arg655Cys) located in the kinase homology domain (KHD).Objectives
To investigate the functional and structural effects of the NPR2 mutation.Methods
Guanylyl cyclase activities of wildtype vs mutant NPR2 were analyzed in transfected HEK 293 cells and in skin fibroblasts. The former were also used to study possible interactions between both isoforms. Homology modeling was performed to understand the molecular impact of the mutation.ResultsCNP stimulated cGMP production by the mutant NPR2 was markedly increased in patient skin fibroblasts and transfected HEK293 cells. The stimulatory effects of ATP on CNP-dependent guanylyl cyclase activity were augmented, suggesting that this novel mutation enhances both the responsiveness of NPR2 to CNP and its allosteric modulation/stabilisation by ATP. Co-immunoprecipitation showed that wildtype and mutant NPR2 can form stable heterodimers, suggesting a dominant positive effect. In accordance with augmented endogenous receptor activity, plasma NTproCNP (a marker of CNP production in tissues) was reduced in the proband.Conclusions
We report the first activating mutation within the KHD of NPR2, resulting in extremely tall stature. Our observations emphasize the important role of this domain in the regulation of guanylyl cyclase activity and bone growth in response to CNP.
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