Atrial natriuretic peptide gene variants and circulating levels: implications in cardiovascular diseases

2014 ◽  
Vol 127 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Speranza Rubattu ◽  
Sebastiano Sciarretta ◽  
Massimo Volpe
Keyword(s):  
Cardiovascular Diseases ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Cardiovascular Health ◽  
Cell Damage ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Gene Variants ◽  
Increased Risk ◽  
Atrial Natriuretic

ANP (atrial natriuretic peptide), discovered 30 years ago in rat cardiac atria, has been extensively investigated with regard to physiology, pathophysiology, cardiovascular disease therapeutics and molecular genetic aspects. Besides its diuretic, natriuretic and vasorelaxant effects, novel properties of this hormone have been described. Thus anti-hypertrophic, anti-fibrotic, anti-proliferative and anti-inflammatory actions suggest that ANP contributes not only to haemodynamic homoeostasis and adjustments, but has also a role in cardiovascular remodelling. Circulating ANP levels represent a valuable biomarker in cardiovascular diseases. ANP structure is highly conserved among species, indicating a key role in cardiovascular health. Thus an abnormal ANP structure may contribute to an increased risk of disease due to altered functions at either the vascular or cardiac level. Among others, the 2238T>C exon 3 variant has been associated with endothelial cell damage and dysfunction and with an increased risk of acute cardiovascular events, a frameshift mutation within exon 3 has been related to increased risk of atrial fibrillation, and ANP gene variants have been linked to increased risk of hypertension in different ethnic groups. On the other hand, the rs5068 variant, falling within the 3′ UTR and associated with higher circulating ANP levels, has been shown to have a beneficial cardioprotective and metabolic effect. Dissecting out the disease mechanisms dependent on specific ANP molecular variants may reveal information useful in the clinical setting for diagnostic, prognostic and therapeutic purposes. Furthermore, insights from molecular genetic analysis of ANP may well integrate advancing knowledge on the role of ANP as a significant biomarker in patients affected by cardiovascular diseases.

scholarly journals The T2238C Human Atrial Natriuretic Peptide Molecular Variant and the Risk of Cardiovascular Diseases

2018 ◽  
Vol 19 (2) ◽  
pp. 540 ◽  
Author(s):  
Speranza Rubattu ◽  
Sebastiano Sciarretta ◽  
Simona Marchitti ◽  
Franca Bianchi ◽  
Maurizio Forte ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Human Atrial Natriuretic Peptide ◽  
Molecular Variant ◽  
Atrial Natriuretic

The Emerging Role of Atrial Natriuretic Peptide in Psychiatry

2020 ◽  
Vol 28 (1) ◽  
pp. 69-79 ◽  
Author(s):  
Donatella Marazziti ◽  
Filippo Maria Barberi ◽  
Federico Mucci ◽  
Alessandra Maglio ◽  
Valerio Dell’Oste ◽  
...  
Keyword(s):  
Immune System ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Hpa Axis ◽  
Cardiovascular Health ◽  
Clinical Samples ◽  
Addictive Behaviors ◽  
Post Traumatic Stress ◽  
Atrial Natriuretic

Introduction: Atrial natriuretic peptide (ANP), composed by 28 amino-acids, is well known to modulate fluid and electrolyte homeostasis, the hypothalamic-pituitary-adrenal (HPA) axis activity and the immune system. Since ANP is produced in both heart and in the central nervous system (CNS), in the last years, increasing attention has been devoted to its possible role in neuropsychiatric disorders. Indeed, scattered data would indicate its possible role in anxiety, major depression, addictive behaviors, post-traumatic stress disorder and other stress-related disorders. Further, ANP has been hypothesized to represent one of the factors linking depression to cardiovascular health and the immune system. Aims: Given the paucity of available information, the aim of this paper was to review the current literature on the role of ANP in the CNS and in the pathophysiology of different neuropsychiatric and stress-related conditions. Discussion: Supporting data on ANP in psychiatric disorders are still limited to animal studies, or to a few “real” findings in patients gathered some decades ago that should be replicated in larger clinical samples. Conclusions: Further studies are necessary to understand the possible implications of ANP in neuropsychiatry, because potentially it might represent a new way for innovative psychopharmacological treatments in different conditions, all underlaid by hyperactive HPA axis.

Prevention of Kupffer cell-induced oxidant injury in rat liver by atrial natriuretic peptide

1999 ◽  
Vol 276 (5) ◽  
pp. G1137-G1144 ◽  
Author(s):  
Manfred Bilzer ◽  
Hartmut Jaeschke ◽  
Angelika M. Vollmar ◽  
Gustav Paumgartner ◽  
Alexander L. Gerbes
Keyword(s):  
Liver Injury ◽  
Inflammatory Response ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Activation ◽  
Cell Damage ◽  
Liver Cells ◽  
Atrial Natriuretic

The generation of reactive oxygen species (ROS) by activated Kupffer cells contributes to liver injury following liver preservation, shock, or endotoxemia. Pharmacological interventions to protect liver cells against this inflammatory response of Kupffer cells have not yet been established. Atrial natriuretic peptide (ANP) protects the liver against ischemia-reperfusion injury, suggesting a possible modulation of Kupffer cell-mediated cytotoxicity. Therefore, we investigated the mechanism of cytoprotection by ANP during Kupffer cell activation in perfused rat livers of male Sprague-Dawley rats. Activation of Kupffer cells by zymosan (150 μg/ml) resulted in considerable cell damage, as assessed by the sinusoidal release of lactate dehydrogenase and purine nucleoside phosphorylase. Cell damage was almost completely prevented by superoxide dismutase (50 U/ml) and catalase (150 U/ml), indicating ROS-related liver injury. ANP (200 nM) reduced Kupffer cell-induced injury via the guanylyl cyclase-coupled A receptor (GCA receptor) and cGMP: mRNA expression of the GCA receptor was found in hepatocytes, endothelial cells, and Kupffer cells, and the cGMP analog 8-bromo-cGMP (8-BrcGMP; 50 μM) was as potent as ANP in protecting from zymosan-induced cell damage. ANP and 8-BrcGMP significantly attenuated the prolonged increase of hepatic vascular resistance when Kupffer cell activation occurred. Furthermore, both compounds reduced oxidative cell damage following infusion of H2O2(500 μM). In contrast, superoxide anion formation of isolated Kupffer cells was not affected by ANP and only moderately reduced by 8-BrcGMP. In conclusion, ANP protects the liver against Kupffer cell-related oxidant stress. This hormonal protection is mediated via the GCA receptor and cGMP, suggesting that the cGMP receptor plays a critical role in controlling oxidative cell damage. Thus ANP signaling should be considered as a new pharmacological target for protecting liver cells against the inflammatory response of activated Kupffer cells without eliminating the vital host defense function of these cells.

Abstract 54: Procalcitonin, Copeptin and Midregional Pro-atrial Natriuretic Peptide as Markers of Ischemic Stroke Risk: The Northern Manhattan Study

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mira Katan ◽  
Yeseon P Moon ◽  
Janet DeRosa ◽  
Myunghee C Paik ◽  
Beat Mueller ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Stroke Risk ◽  
Hemodynamic Stress ◽  
Increased Risk ◽  
Ischemic Stroke Risk ◽  
Atrial Natriuretic

Background: Chronic infections and neuroendocrine dysfunction may be risk factors for ischemic stroke. We hypothesized that selected blood biomarkers of infection (procalcitonin, or PCT), hypothalamic-pituitary-axis function (copeptin), and hemodynamic stress (midregional pro-atrial natriuretic peptide, or MRproANP) would be associated with incident ischemic stroke risk in the multi-ethnic, urban Northern Manhattan Study (NOMAS) cohort. Methods: A case-cohort study was performed among initially stroke-free participants from the prospective population-based NOMAS study. The mean follow up was 11 years. Cases were defined as first ischemic stroke (including fatal) with available baseline blood (n=172). We randomly selected controls among those who did not develop an event (n=344). Biomarkers were measured in a blinded batch analysis (Laboratory of the Medical University Clinic, Aarau, Switzerland, using B.R.A.H.M.S assays by Thermo Fisher Scientific). We calculated hazard ratios and 95% confidence intervals (HR, 95% CI) using Cox proportional hazards models, with inverse probability weighting to correct for the case-cohort study design, to estimate the association with risk of stroke after adjusting for demographic, behavioral, and medical risk factors. Results: Mean age of cases was 72 (IQR 65-78); 59% were female. After full adjustment, those with PCT in the top quartile, compared to the lowest quartile, were at increased risk of ischemic stroke (adjusted HR 1.98, 95% CI 1.02-3.83). Those with MRproANP levels in the top quartile, compared to the lowest quartile, were also at increased risk of stroke (adjusted HR 3.45, 95% CI 1.58-7.52), but not those with higher copeptin levels. The distribution of MRproANP differed by stroke etiology. Levels of MRproANP were greater for cardioembolic strokes (CE), and MRproANP levels were predictive of CE (adjusted HR 3.29 per SD, 95% CI 1.89-5.72). Conclusion: Higher levels of procalcitonin, a marker of infection, and MRproANP, a marker for hemodynamic stress, were independently associated with ischemic stroke risk in this multiethnic, urban cohort. MRproANP was specifically associated with cardioembolic stroke risk. Further study is needed to confirm these results.

scholarly journals Effect of liraglutide on atrial natriuretic peptide, adrenomedullin, and copeptin in PCOS

2018 ◽  
Vol 7 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Signe Frøssing ◽  
Malin Nylander ◽  
Caroline Kistorp ◽  
Sven O Skouby ◽  
Jens Faber
Keyword(s):  
Insulin Resistance ◽  
Heart Rate ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Visceral Fat ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Increased Risk ◽  
Risk Biomarkers ◽  
Atrial Natriuretic

Context Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP. Objective To investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin. Methods Seventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined. Results Baseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45–0.56) nmol/L, MR-proANP 44.8 (34.6–56.7) pmol/L and copeptin 4.95 (3.50–6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM −6% (−11 to 2, P = 0.058), MR-proANP −25% (−37 to −11, P = 0.001) and copeptin +4% (−13 to 25, P = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate. Conclusion In an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently associated with an increase in the heart rate.

Sign in / Sign up

Export Citation Format

Share Document