atrial-natriuretic-factor and Atrial-Remodeling

Investigations into the mixed muscle-secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones - the natriuretic peptides - referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Topics: Animals; Atrial Appendage; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Cyclic GMP; Diabetes Mellitus; Fibrosis; Gene Expression Regulation, Developmental; Heart Atria; Heart Failure; Humans; Hypertension; Lipid Metabolism; Metabolic Syndrome; Mice; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Prognosis; Protein Processing, Post-Translational; Pulmonary Arterial Hypertension; Receptors, Guanylate Cyclase-Coupled; Secretory Vesicles; Ventricular Remodeling; Water-Electrolyte Balance

Atrial natriuretic peptide (ANP) deficiency is thought to be one of the causes of heart failure induced by atrial fibrillation (AF). Although ANP deficiency is thought to occur as a result of atrial remodeling, data to explain this mechanism are limited. The purpose of this study was to investigate the association between ANP and left atrial remodeling or prognosis of heart failure in patients with AF ablation.. In total, 373 consecutive patients who underwent initial ablation for persistent AF [age, 67 ± 10 years; female, 97 (26%)] were retrospectively enrolled. ANP and brain natriuretic peptide (BNP) were measured before the procedure and the ANP/BNP ratio was calculated. Left atrial volume index, left atrial appendage emptying velocity, and left atrial low-voltage areas (LVAs) were used as left atrial-remodeling parameters. The primary outcome of heart failure was defined as the composite of all-cause death or hospitalization due to worsening heart failure.. The median ANP level was 116 (71-178) pg/ml and the median ANP/BNP ratio was 0.65 (0.46-1.00). The ANP/BNP ratio decreased with increasing left atrial volume index or LVAs and with decreasing left atrial appendage emptying velocity. During the 5-year follow-up, freedom from the primary outcome was significantly lower in patients with ANP/BNP ratio ≤0.65 than in those with ANP/BNP ratio >0.65 (84.6% versus 95.6%, P  < 0.01).. Secretion of ANP relative to BNP decreased with progression of left atrial remodeling in patients with AF ablation. Furthermore, prognosis of heart failure was poor in patients with a low ANP/BNP ratio.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies

Myocardial remodeling is a complex pathological process and its mechanism is unclear. The present study investigated whether epigallocatechin gallate (EGCG) prevents myocardial remodeling by regulating histone acetylation and explored the mechanisms underlying this effect in the heart of a mouse model of transverse aortic constriction (TAC). A TAC mouse model was created by partial thoracic aortic banding (TAB). Subsequently, TAC mice were injected with EGCG at a dose of 50 mg/kg/day for 12 weeks. The hearts of mice were collected for analysis 4, 8 and 12 weeks after TAC. Histopathological changes in the heart were observed by hematoxylin and eosin, Masson trichrome and wheat germ agglutinin staining. Protein expression levels were investigated using western blotting. Cardiac function of mice was detected by echocardiography. The level of histone acetylated lysine 27 on histone H3 (H3K27ac) first increased and then decreased in the hearts of mice at 4, 8 and 12 weeks after TAC. The expression levels of two genes associated with pathological myocardial remodeling, atrial natriuretic peptide (

Topics: Acetylation; Animals; Atrial Natriuretic Factor; Atrial Remodeling; Catechin; Constriction; Disease Models, Animal; Electrocardiography; Heart Failure; Histone Deacetylases; Histones; Lysine; Male; MEF2 Transcription Factors; Natriuretic Peptide, Brain; Survival Rate; Ventricular Remodeling

Measures of structural and functional remodelling of the left atrium (LA) are emerging as useful biomarkers in heart failure (HF). We hypothesized that LA volume and its contribution to stroke volume (SV) would predict a composite endpoint of HF hospitalization or death in patients with HF.. We recruited 57 controls and 86 patients with HF, including preserved and reduced left ventricular ejection fraction (LVEF). Cardiac magnetic resonance imaging was used to evaluate LA volumes and contribution to LV SV. Plasma mid-region pro-atrial natriuretic peptide (MR-proANP) was evaluated. LA volume was negatively correlated with LVEF (P = 0.001) and positively correlated with LV mass in HFrEF (P < 0.001) but not in HFpEF. LA volume at end-diastole was associated with the composite endpoint in HFrEF (hazard ratio 1.26, 95% confidence interval 1.01-1.54; P = 0.044), but not HFpEF (1.06, 0.85-1.30; P = 0.612), per 10 mL/m increase. Active contribution to SV was negatively associated with the composite endpoint in HFpEF (0.32, 0.14-0.66; P = 0.001), but not HFrEF (0.91, 0.38-2.1; P = 0.828) per 10% increase. MR-proANP was associated with the composite endpoint in HFpEF (1.46, 1.03-1.94; P = 0.034), but not in HFrEF (1.14, 0.88-1.37; P = 0.278), per 100 pM increase.. We found different relationships between LA remodelling and biomarkers in HFrEF and HFpEF. Our results support the hypothesis that the pathophysiologic underpinnings of HFpEF and HFrEF are different, and atrial remodelling encompasses distinct components for each HF subtype.

Topics: Atrial Natriuretic Factor; Atrial Remodeling; Heart Failure; Humans; Prognosis; Stroke Volume; Ventricular Function, Left

Topics: Albuminuria; Animals; Atrial Natriuretic Factor; Atrial Remodeling; Blood Pressure; Cardiomegaly; Cardiotonic Agents; Dinoprostone; Drug Evaluation, Preclinical; Fibrosis; Glomerular Filtration Rate; Heart; Hypertension; Kidney; Kidney Diseases; Male; Myocytes, Cardiac; Natriuresis; Peptide Fragments; Potassium; Rats; Rats, Inbred Dahl; Smad2 Protein; Sodium Chloride, Dietary; Ventricular Remodeling

Low voltage areas (LVAs) represent advanced remodelling processes in left atrium in patients with atrial fibrillation (AF) and are associated with higher rates of arrhythmia recurrences. However, the prediction of LVA based on clinical parameters is understudied. Recently, we introduced APPLE score to predict rhythm outcomes after catheter ablation. The aim of this study was to analyse (i) LVA prediction using APPLE score and (ii) differences in biomarker profiles according to APPLE score in AF patients.. Patients undergoing first AF ablation were included. The APPLE score (one point for Age >65 years, Persistent AF, imPaired eGFR <60 mL/min/1.73 m2, LA diameter ≥43 mm, EF <50%) was calculated before ablation. Blood plasma samples from femoral vein were collected before ablation. Low voltage area were determined using high-density maps and defined as <0.5 mV. NT-proANP, NT-proBNP, L-Selectin, and vascular cell adhesion protein 1 (VCAM-1) were studied using commercially available assays. We studied 214 patients [age median (interquartile range) 65 (57-72) years, 59% males, 59% persistent AF, 27% LVA]. There were 42% patients with APPLE ≥3. The levels of NT-proANP (P < 0.001), NT-proBNP (P = 0.016), and VCAM-1 (P = 0.040) increased with each APPLE point. In the univariable analysis, APPLE score [odds ratio (OR) 1.921, 95% confidence interval (CI) 1.453-2.538; P < 0.001], female gender (OR 2.283, 95% CI 1.280-4.071; P = 0.005), and NT-proANP (OR 1.031, 95% CI 1.008-1.054; P = 0.007) were significant predictors for LVA. On the multivariable analysis, only APPLE score and female gender remained associated with LVA.. The APPLE score can be used for prediction of LVA before AF ablation. There was a positive correlation between biomarker levels and APPLE score.

Topics: Action Potentials; Age Factors; Aged; Atrial Fibrillation; Atrial Function, Left; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Catheter Ablation; Decision Support Techniques; Female; Glomerular Filtration Rate; Heart Rate; Humans; Kidney; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Pulmonary Veins; Recurrence; Risk Assessment; Risk Factors; Sex Factors; Time Factors; Treatment Outcome; Vascular Cell Adhesion Molecule-1

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Catheter Ablation; Female; Heart Atria; Heart Diseases; Humans; Hypertension; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Veins; Tomography, X-Ray Computed; Troponin T; Vascular Remodeling

Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets.

Topics: Adipocytes; Animals; Atrial Natriuretic Factor; Atrial Remodeling; Bucladesine; Cardiomegaly; Cell Differentiation; Diastole; Fibroblast Growth Factors; Hepatocyte Growth Factor; Isoproterenol; Male; Myoblasts, Skeletal; Myocardial Contraction; Myocardial Infarction; Myocardium; Organ Culture Techniques; Paracrine Communication; Pyridazines; Rats; Rats, Inbred Lew; Stem Cell Transplantation; Stem Cells; Systole; Vascular Endothelial Growth Factor A

Studies of left atrial (LA) function, until the latter part of the 20th century, were mostly limited to experimental animal models and to studies related to clinical research in the cardiac catheterization laboratory. For this reason, LA function has received considerably less attention than left ventricular (LV) functions, even though evidence suggests that LA myopathy and failure may exist as an isolated entity, precede and/or coexist with LV myopathy. The introduction of echocardiography and Doppler echocardiography in clinical practice has contributed significantly to our understanding of LA function and its interrelationships with the LV, aorta, pulmonary artery and other parts of the cardiovascular system. In addition, LA with the secretion of atrial natriuretic peptides is playing an important role in cardiovascular and neurohumoral homeostasis. Today, it is well known that LA structural and functional abnormalities that are present in many diseases and disorders constitute a powerful prognostic indicator. As technology (echocardiography, magnetic resonance imaging, computed tomography and others) continues to evolve, it is expected that, in the near future, LA structure and function will be routinely used as LV function is used today.

Topics: Atrial Function, Left; Atrial Natriuretic Factor; Atrial Remodeling; Cardiac Imaging Techniques; Heart Atria; Heart Diseases; Humans

Endurance athletes have an increased risk of atrial fibrillation. We performed a longitudinal study on elite runners of the 2010 Jungfrau Marathon, a Swiss mountain marathon, to determine acute effects of long-distance running on the atrial myocardium. Ten healthy male athletes were included and examined 9 to 1 week prior to the race, immediately after, and 1, 5, and 8 days after the race. Mean age was 34.9 ± 4.2 years, and maximum oxygen consumption was 66.8 ± 5.8 mL/kg*min. Mean race time was 243.9 ± 17.7 min. Electrocardiographic-determined signal-averaged P-wave duration (SAPWD) increased significantly after the race and returned to baseline levels during follow-up (128.7 ± 10.9 vs. 137.6 ± 9.8 vs. 131.5 ± 8.6 ms; P < 0.001). Left and right atrial volumes showed no significant differences over time, and there were no correlations of atrial volumes and SAPWD. Prolongation of the SAPWD was accompanied by a transient increase in levels of high-sensitivity C-reactive protein, proinflammatory cytokines, total leucocytes, neutrophil granulocytes, pro atrial natriuretic peptide and high-sensitivity troponin. In conclusion, marathon running was associated with a transient conduction delay in the atria, acute inflammation and increased atrial wall tension. This may reflect exercise-induced atrial myocardial edema and may contribute to atrial remodeling over time, generating a substrate for atrial arrhythmias.

Topics: Adult; Atrial Natriuretic Factor; Atrial Remodeling; C-Reactive Protein; Electrocardiography; Heart Atria; Humans; Inflammation; Interleukin-6; Leukocyte Count; Longitudinal Studies; Male; Neutrophils; Prospective Studies; Running; Troponin; Tumor Necrosis Factor-alpha; Ultrasonography

Atrial fibrillation (AF) often occurs in the presence of an underlying disease. These underlying diseases cause atrial remodelling, which make the atria more susceptible to AF. Stretch is an important mediator in the remodelling process. The aim of this study was to develop an atrial cell culture model mimicking remodelling due to atrial pressure overload. Neonatal rat atrial cardiomyocytes (NRAM) were cultured and subjected to cyclical stretch on elastic membranes. Stretching with 1 Hz and 15% elongation for 30 min. resulted in increased expression of immediate early genes and phosphorylation of Erk and p38. A 24-hr stretch period resulted in hypertrophy-related changes including increased cell diameter, reinduction of the foetal gene program and cell death. No evidence of apoptosis was observed. Expression of atrial natriuretic peptide, brain natriuretic peptide and growth differentiation factor-15 was increased, and calcineurin signalling was activated. Expression of several potassium channels was decreased, suggesting electrical remodelling. Atrial stretch-induced change in skeletal α-actin expression was inhibited by pravastatin, but not by eplerenone or losartan. Stretch of NRAM results in elevation of stress markers, changes related to hypertrophy and dedifferentiation, electrical remodelling and cell death. This model can contribute to investigating the mechanisms involved in the remodelling process caused by stretch and to the testing of pharmaceutical agents.

Topics: Actins; Animals; Animals, Newborn; Anticholesteremic Agents; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Calcineurin; Cell Death; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Developmental; Growth Differentiation Factor 15; Heart Atria; Myocytes, Cardiac; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Potassium Channels; Pravastatin; Pressure; Rats; Rats, Sprague-Dawley; Signal Transduction; Stress, Mechanical

We have previously demonstrated that catheter-based renal sympathetic denervation (RSD) could suppress atrial fibrillation (AF) in canines with short-time rapid right atrial pacing (RAP). However, the role of renal denervation on atrial remodeling is unclear. The aim of the present study was to explore the long-term effect of RSD on the atrial remodeling during prolonged RAP. Twenty mongrel dogs were implanted with a high-frequency cardiac pacemaker with a transvenous lead inserted into the right atrial appendage. The dogs were divided into three groups: a sham-operated group (n = 6), the chronic RAP (CRAP) group (n = 7), and the CRAP+RSD group (n = 7). In the CRAP+RSD group, a pacemaker was implanted 6 weeks after RSD was performed bilaterally for recovery. RAP was maintained for 5 weeks in CRAP group and CRAP+RSD group. The plasma levels of Angiotensin II and aldosterone were significantly increased in CRAP group compared with sham-operated group, but the increasing trend was inhibited in CRAP+RSD group compared with CRAP group (P<0.05). Similarly, RSD suppressed the increasing trend that prolonged RAP produced in the left atrial levels of ANP, TNF-α and IL-6. Compared with the sham-operated group, the CRAP group had significantly increased levels of caspase-3, bax and Cx40 whereas the level of Bcl-2 decreased (P<0.05). RSD markedly reduced the upregulation of caspase-3, bax and Cx40 and the downregulation of Bcl-2 expression compared with the CRAP group (P<0.05). Picric acid-sirius red staining study suggested that RSD could markedly alleviate the lesion degree of cardic fibrosis induced by CRAP (P<0.05). Immunohistochemistry results showed that the densities of TH- and GAP43- positive nerves were significantly elevated in the CRAP group compared with the sham-operated group, while RSD operation signicantly inhibited the these changes produced by CRAP. These findings suggest that renal denervation could suppress the atrial remodeling after prolonged RAP in ambulatory canines.

Topics: Aldosterone; Angiotensin II; Animals; Apoptosis; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Blood Pressure; Cardiac Pacing, Artificial; Dogs; Fibrosis; Gap Junctions; GAP-43 Protein; Heart Atria; Inflammation; Interleukin-6; Kidney; Myocytes, Cardiac; Sympathectomy; Tumor Necrosis Factor-alpha