natriuretic-peptide--brain and Pulmonary-Fibrosis

Pulmonary hypertension (PH) can develop in lung fibrosis, and contributes to increased morbidity and mortality. Noninvasive parameters in the evaluation of PH in lung disease could aid in the management of these subjects. In this study, we aimed to characterize the role of brain natriuretic peptide (BNP) and the six-minute walk distance (6-MWD) in the assessment of pulmonary hypertension (PH) in subjects with lung fibrosis. Subjects with lung fibrosis and elevated BNP levels (n = 20) had significantly more severe PH during right heart catheterization than those with lung fibrosis, and normal BNP levels (mean pulmonary arterial pressure (40.85 +/- 3.2 mm Hg vs. 23.42+/-1.44 mm Hg, respectively) (n = 19) (p < 0.001). Significant correlations between lung volumes and BNP concentrations were not observed. A weak correlation existed between capillary pO(2) and 6-MWD (r = 0.42; p < 0.001). The presence of moderate-severe PH was associated with significant reduction of the 6-MWD. BNP concentrations predicted moderate-severe PH with 100% sensitivity and high specificity (89%). We conclude that BNP is an excellent marker for the presence of PH in patients with lung fibrosis. In addition, our data suggest that PH contributes significantly to exercise limitation in patients with severe lung fibrosis, raising the possibility that treatment of PH may be beneficial in these patients.

Topics: Biomarkers; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Respiratory Function Tests; Sensitivity and Specificity

Expression of miR-154 is upregulated in the diseased heart and was previously shown to be upregulated in the lungs of patients with pulmonary fibrosis. However, the role of miR-154 in a model of sustained pressure overload-induced cardiac hypertrophy and fibrosis had not been assessed. To examine the role of miR-154 in the diseased heart, adult male mice were subjected to transverse aortic constriction for four weeks, and echocardiography was performed to confirm left ventricular hypertrophy and cardiac dysfunction. Mice were then subcutaneously administered a locked nucleic acid antimiR-154 or control over three consecutive days (25 mg/kg/day) and cardiac function was assessed 8 weeks later. Here, we demonstrate that therapeutic inhibition of miR-154 in mice with pathological hypertrophy was able to protect against cardiac dysfunction and attenuate adverse cardiac remodelling. The improved cardiac phenotype was associated with attenuation of heart and cardiomyocyte size, less cardiac fibrosis, lower expression of atrial and B-type natriuretic peptide genes, attenuation of profibrotic markers, and increased expression of p15 (a miR-154 target and cell cycle inhibitor). In summary, this study suggests that miR-154 may represent a novel target for the treatment of cardiac pathologies associated with cardiac fibrosis, hypertrophy and dysfunction.

Topics: Animals; Aorta; Atrial Natriuretic Factor; Cyclin-Dependent Kinase Inhibitor p15; Disease Models, Animal; Echocardiography; Hypertension; Hypertrophy, Left Ventricular; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Natriuretic Peptide, Brain; Oligonucleotides; Pulmonary Fibrosis; Ventricular Remodeling

Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo.. Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests.. Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups.. Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Topics: Animals; Bleomycin; Hydroxyproline; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung Compliance; Male; Motor Activity; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Random Allocation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Simvastatin

To evaluate the relationship between pulmonary and myocardial fibrosis in patients with systemic sclerosis (SS).. Eighteen patients with SS prospectively underwent cardiac magnetic resonance imaging (CMR) and high-resolution computed tomography (HRCT) of the chest. Cardiac biomarkers (N-terminal pro B-type natriuretic peptide) and quality-of-life measures (SF-36 and SS health assessment questionnaires) were assessed. Two readers blinded to other test results evaluated the CMRs in consensus for functional left and right ventricular parameters and for myocardial late enhancement. HRCT images were reviewed at 5 levels and scored for total disease extent, extent of reticulation, proportion of ground-glass opacities (GGO), and coarseness of reticulation.. Right ventricular ejection fraction correlated significantly with the percentage of late enhancement of the myocardium (R=0.63, P<0.01), extent of pulmonary fibrosis (R=0.57, P<0.01), and extent of GGO (R=0.53, P<0.05). Significant correlations were also found between the percentage of late enhancement of the myocardium and the extent of overall pulmonary fibrosis (R=0.59, P<0.05) and the extent of the ground-glass subcomponent (R=0.58, P<0.05). N-terminal pro B-type natriuretic peptide correlated significantly with the number of myocardial segments with late enhancement (R=0.64, P<0.05). Stepwise multiple linear regression revealed the extent of pulmonary GGO to be the only independent predictor of the percentage of myocardial enhancement (R2=0.61, P<0.0001).. In patients with SS with pulmonary fibrosis on HRCT images, CMR may be a useful test to detect early-stage myocardial fibrosis.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Cardiomyopathies; Case-Control Studies; Contrast Media; Endomyocardial Fibrosis; Female; Gadolinium DTPA; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Fibrosis; Quality of Life; Regression Analysis; Scleroderma, Systemic; Surveys and Questionnaires; Tomography, X-Ray Computed

Pulmonary hypertension (PH) is an important complication to interstitial lung disease (ILD). The aim of the present study was to investigate the relation of NT-proBNP, fibrin D-dimer, troponin-T, uric acid and exhaled nitric oxide (NO) to the presence of PH and mortality in ILD.. In a previously described cohort of 212 ILD patients of whom 29 had PH, levels of the above mentioned biomarkers were analyzed as routine tests.. A value of NT-proBNP below 95 ng/l had a negative predictive value for PH of 99% (95% CI: 94-100). Values of troponin-T were higher in patients with PH (median (inter quartile range) = 9 (9-20) vs. 9(9-10) ng/l), and the odds ratio (OR) for PH was increased in patients with abnormal levels of uric acid (OR (95% CI) = 3.1(1.1-8.8)). NT-proBNP and troponin-T values above the 50(th) percentile, and uric acid and fibrin D-dimer values above the 90th percentile were each associated with increased mortality.. A value of NT-proBNP below 95 ng/l may be used as a rule-out test for PH in ILD, while an abnormal value of uric acid is a risk factor for PH. NT-proBNP, troponin-T, uric acid and fibrin D-dimer have prognostic value in ILD patients, while exhaled levels of NO do not seem to predict PH or mortality.

Topics: Biomarkers; Cross-Sectional Studies; Fibrin Fibrinogen Degradation Products; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Natriuretic Peptide, Brain; Nitric Oxide; Peptide Fragments; Prognosis; Pulmonary Fibrosis; ROC Curve; Troponin T; Uric Acid

Topics: Biomarkers; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Sensitivity and Specificity

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Natriuretic Peptide, Brain; Piperazines; Pulmonary Fibrosis; Purines; Raynaud Disease; Scleroderma, Systemic; Sildenafil Citrate; Sulfones