natriuretic-peptide--brain and Endomyocardial-Fibrosis

Myocardial fibrosis, progressive over-accumulation of extracellular matrix (ECM) components in cardiac muscle, defined as a key component of heart failure and since then various studies showed a strong connection between fibrosis and progression of heart failure. The impaired left ventricular diastolic and systolic functions that are originated by fibrosis are used to predict poor clinical outcome in dilated cardiomyopathy. Even though endomyocardial biopsy is still considered as a gold standard, various noninvasive imaging techniques have been used to detect presence, location and extend of myocardial fibrosis. Cardiac magnetic resonance emerged as a crucial noninvasive imagining technique because of its high accuracy and high fidelity in detection of fibrosis. The noninvasive assessment of fibrosis is advantageous in early prediction of possible adverse outcomes and creates an opportunity to utilize new therapeutic approaches that target fibrosis in heart failure.

Topics: Endomyocardial Fibrosis; Heart Failure; Heart Failure, Diastolic; Humans; Magnetic Resonance Imaging; Myocardium; Natriuretic Peptide, Brain; Prognosis; Ventricular Remodeling

Topics: Aldosterone; Animals; Cardiotonic Agents; Disease Progression; Dose-Response Relationship, Drug; Endomyocardial Fibrosis; Heart Failure; Humans; Natriuretic Peptide, Brain; Natriuretic Peptides; Sodium; Treatment Outcome; Ventricular Remodeling

We attempted to test the hypothesis that chronic angiotensin II type 1A receptor blockade (ARB) alters myocardial collagen turnover leading to an improvement of diastolic dysfunction in diabetic patients.. Forty-eight type 2 diabetic patients were divided into 2 groups: 38 treated with candesartan for 6 months, and 10 without candesartan, as controls. Doppler mitral flow velocity pattern and biomarkers of collagen type I turnover were assessed before and after ARB during a 6-month period. The mitral E/A ratio increased from 0.65+/-0.11 to 0.75+/-0.19. The carboxy-terminal propeptide of procollagen type I (PIP), an index of collagen type I synthesis, decreased and the carboxy-terminal telopeptide of collagen type I (CITP), an index of collagen type I degradation, increased following ARB. Consequently, the PIP/CITP ratio, an index of coupling between the synthesis and degradation of collagen type I, decreased. None of the indexes changed in the control group. The change in left ventricular chamber stiffness did not correlate with the change in PICP (r=0.08, p=NS), but it did with the changes in CITP or in the PIP/CITP ratio (r=0.35, p<0.05; r=0.39, p<0.05).. Chronic ARB improves diastolic dysfunction in diabetic patients, at least partially through the attenuation of myocardial fibrosis, by regulating collagen turnover, particularly by facilitating collagen degradation.

Topics: Aged; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Collagen; Diabetes Mellitus, Type 2; Endomyocardial Fibrosis; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles; Ventricular Dysfunction, Left

We sought to evaluate the effects of spironolactone on neurohumoral factors and left ventricular remodeling in patients with congestive heart failure (CHF).. Aldosterone (ALD) promotes collagen synthesis and structural remodeling of the heart. Spironolactone, an ALD receptor antagonist, is reported to reduce mortality in patients with CHF, but its influence on left ventricular remodeling has not been clarified.. Thirty-seven patients with mild-to-moderate nonischemic CHF were randomly divided into two groups that received treatment with spironolactone (n = 20) or placebo (n = 17). We measured left ventricular volume and mass before treatment and after four months of treatment. We also measured the plasma levels of neurohumoral factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), as well as plasma procollagen type III aminoterminal peptide (PIIINP), a marker of myocardial fibrosis.. Left ventricular volume and mass were significantly decreased and ejection fraction was significantly increased in the spironolactone group, while there were no changes in the placebo group. Plasma levels of ANP, BNP and PIIINP were significantly decreased after spironolactone treatment, but were unchanged in the placebo group. There was a significant positive correlation between the changes of PIIINP and changes of the left ventricular volume index (r = 0.45, p = 0.045) as well as the left ventricular mass index (r = 0.65, p = 0.0019) with spironolactone treatment.. These findings indicate that four months of treatment with spironolactone improved the left ventricular volume and mass, as well as decreased plasma level of BNP, a biochemical marker of prognosis and/or ventricular hypertrophy, suggesting that endogenous aldosterone has an important role in the process of left ventricular remodeling in nonischemic patients with CHF.

Topics: Aged; Aldosterone; Cardiac Volume; Endomyocardial Fibrosis; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prospective Studies; Spironolactone; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling

Myocardial dysfunction and heart failure (HF) are increased in rheumatoid arthritis (RA), yet there are few studies of the myocardium in RA.. RA patients with no known heart disease or risk factors underwent gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Images were assessed for left-ventricular (LV) structural and functional parameters and for myocardial late gadolinium enhancement (LGE; an indicator of myocardial fibrosis) and T2-weighted imaging (an indicator of active inflammation). We modeled the associations between RA characteristics and N-terminal pro-brain natriuretic protein (NT-proBNP) levels with LGE and T2-weighted imaging. We also assessed whether LGE and/or T2-weighted imaging were associated with abnormal LV structure or dysfunction.. A total of 60 RA patients were studied. LGE was present in 19 (32%) and T2-weighted imaging in 7 (12%), 5 of whom also had LGE. After adjustment for relevant confounders, higher odds of LGE with each swollen joint (odds ratio [OR] 1.87, P = 0.008), each log unit higher C-reactive protein level (OR 3.36, P = 0.047), and each log unit higher NT-proBNP (OR 20.61, P = 0.009) were found. NT-proBNP was also significantly higher (135%) among those with T2-weighted imaging than in those without T2-weighted imaging or LGE. Higher LV mass index and LV mass:end diastolic volume ratio were observed in those with T2-weighted imaging than in those with no myocardial abnormalities and in those with LGE without T2-weighted imaging; however, ejection fraction was not reduced in those with either LGE or T2-weighted imaging.. These data suggest that cardiac MRI findings indicating myocardial inflammation/fibrosis are correlated with RA disease activity and alterations in myocardial structure known to precede clinical HF.

Topics: Adult; Aged; Arthritis, Rheumatoid; C-Reactive Protein; Contrast Media; Endomyocardial Fibrosis; Female; Gadolinium DTPA; Heart; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Risk Factors

The relationship between microvascular dysfunction and plasma B-type natriuretic peptide (BNP) levels remains unclear in heart failure (HF) patients with cardiac fibrosis.. This study evaluated 55 consecutive non-ischemic HF patients in an effort to determine the relationship between endothelial independent coronary microvascular dysfunction and plasma BNP levels, as well as whether each measure is correlated with myocardial fibrosis. We evaluated plasma BNP levels in patients with stable HF. We used cardiac catheterization to measure trans-cardiac BNP release levels, measuring from the coronary sinus and the aortic root, and coronary flow reserve (CFR). Patients also underwent cardiac magnetic resonance imaging to evaluate for the presence of late gadolinium enhancement (LGE), as an indicator of cardiac fibrosis.. CFR in cardiac catheterization was significantly and inversely correlated with plasma BNP levels (r=0.336, p=0.012) and trans-cardiac BNP release levels (r=0.347, p=0.041). Thirty-three patients were LGE-positive. CFR was significantly correlated with plasma BNP levels in the LGE-positive group (r=0.349, p=0.046), but this correlation was not significant in the LGE-negative group. (r=0.338, p=0.125). Multivariate logistic regression analysis revealed that a plasma BNP levels >180pg/ml at stable HF condition was significant and independent predictor of CFR<2.5 in all patients (p=0.035, odds ratio: 5.2, 95% confidence interval: 1.1-29.0), and in the LGE-positive group (p=0.040, odds ratio: 5.4, 95% confidence interval: 1.1-27.2).. In non-ischemic HF patients especially those with cardiac fibrosis, endothelial independent microvascular dysfunction is closely correlated with plasma BNP levels, and ventricular wall tension.

Topics: Adult; Aged; Cardiac Catheterization; Cohort Studies; Coronary Circulation; Endomyocardial Fibrosis; Female; Heart Failure; Humans; Male; Microvessels; Middle Aged; Natriuretic Peptide, Brain

Sympathetic activation and parasympathetic withdrawal are important characteristics of heart failure. Recent studies demonstrate that galanin reduces the discharge of acetylcholine and inhibits vagal bradycardia by acting on galanin receptor type 1 (GalR1). We speculated that blocking GalR1 is beneficial for heart failure.. Rats with heart failure were induced by myocardial infarction. The rats were injected intraperitoneally with galanin receptor antagonist M40 solution (30 nmol/kg) or saline for 4 weeks. Cardiac function was assessed by echocardiography and brain natriuretic peptide (BNP) in plasma. The ratio of heart weight to body weight (HW/BW), hematoxylin-eosin (HE), and Masson trichrome stain was used to evaluate cardiac remodeling. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) in plasma, and sarco(endo)plasmic reticulum Ca(2+) -ATPase (SERCA2) in heart tissue were detected to confirm the mechanism of the cardioprotection effect.. Compared with rats injected with saline, M40 effectively improved cardiac function of contraction; decreased BNP, IL-6, and HW/BW (all P < 0.05); attenuated cardiac fibrosis; and upregulated SERCA2 (P < 0.05).. M40 improves cardiac function and attenuates remodeling, suggesting that galanin receptor antagonist may be a potential therapeutic agent for HF.

Topics: Animals; Cardiotonic Agents; Coloring Agents; Disease Models, Animal; Electrocardiography; Endomyocardial Fibrosis; Enzyme-Linked Immunosorbent Assay; Galanin; Heart Failure; Interleukin-6; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Galanin; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Tumor Necrosis Factor-alpha; Ventricular Remodeling

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

Cardiac fibrosis is common and associated with poor prognosis in patients with heart failure. We investigated the effect of cardiac fibrosis on the left ventricular (LV) diastolic function, functional capacity, LV remodeling, and biochemical parameters in patients with nonischemic dilated cardiomyopathy (NIDC). In addition, we investigated the biochemical and echocardiographic predictors of cardiac fibrosis in this group.. Forty patients with NIDC were enrolled. Cardiac fibrosis was evaluated according to the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Nineteen patients had cardiac fibrosis (Group I) and 21 patients did not have cardiac fibrosis (Group II). LV systolic and diastolic parameters were assessed with conventional and tissue Doppler echocardiography. N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels of each patient were recorded. Patients with cardiac fibrosis had impaired diastolic function, higher functional class and NT-pro BNP levels, and significant LV remodeling than the patients without cardiac fibrosis. A correlation analysis revealed that the cardiac fibrosis severity was associated with functional class, cardiac chamber sizes, NT-pro BNP levels, diastolic parameters such as E/Se. A linear regression analysis demonstrated that NT-pro BNP and E/Se were the independent predictors of cardiac fibrosis.. Cardiac fibrosis correlates with impaired LV diastolic function and functional capacity, elevated NT-proBNP levels, and adverse cardiac remodeling in patients with NIDC. Therefore, the assessment of cardiac fibrosis can be useful in the management of these patients.

Topics: Cardiomyopathy, Dilated; Echocardiography; Endomyocardial Fibrosis; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left; Ventricular Remodeling

Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for volume-overloaded heart failure or sham surgery. All rats with a fistula received either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by gavage. Two weeks later, the LS diet significantly increased the plasma aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1% with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial fibrosis in fistula-created rats was more prominent with the LS diet than with the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on the LS diet expressed significantly increased oxidative stress and transforming growth factor-beta compared with those on the NS diets (P<0.05). These increases in the fistula-created rats on the LS diet were significantly suppressed by the non-hypotensive dose of spironolactone (P<0.05). These results suggest that increased plasma aldosterone level with strict salt restriction activated the mineralocorticoid receptor signaling in volume-overloaded condition, resulting in increased myocardial fibrosis.

Topics: Aldosterone; Animals; Atrial Natriuretic Factor; Body Weight; Cell Size; Contraindications; Diet, Sodium-Restricted; Endomyocardial Fibrosis; Heart; Heart Failure; Hemodynamics; Hypertension; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; Signal Transduction; Spironolactone; Transforming Growth Factor beta; Tyrosine; Ventricular Remodeling

Constrictive pericarditis (CP) and restrictive cardiomyopathy share many similarities in both their clinical and hemodynamic characteristics and N-terminal prohormone brain natriuretic peptide (NT-proBNP) is a sensitive marker of cardiac diastolic dysfunction. The objectives of the present study were to determine whether serum NT-proBNP was high in patients with endomyocardial fibrosis (EMF) and CP, and to investigate how this relates to diastolic dysfunction. Thirty-three patients were divided into two groups: CP (16 patients) and EMF (17 patients). The control group consisted of 30 healthy individuals. Patients were evaluated by bidimensional echocardiography, with restriction syndrome evaluated by pulsed Doppler of the mitral flow and serum NT-proBNP measured by immunoassay and detected by electrochemiluminescence. Spearman correlation coefficient was used to analyze the association between log NT-proBNP and echocardiographic parameters. Log NT-proBNP was significantly higher (P < 0.05) in CP patients (log mean: 2.67 pg/mL; 95%CI: 2.43-2.92 log pg/mL) and in EMF patients (log mean: 2.91 pg/mL; 95%CI: 2.70-3.12 log pg/mL) compared with the control group (log mean: 1.45; 95%CI: 1.32-1.60 log pg/mL). There were no statistical differences between EMF and CP patients (P = 0.689) in terms of NT-proBNP. The NT-proBNP log tended to correlate with peak velocity of the E wave (r = 0.439; P = 0.060, but not with A wave (r = -0.399; P = 0.112). Serum NT-proBNP concentration can be used as a marker to detect the presence of diastolic dysfunction in patients with restrictive syndrome; however, serum NT-proBNP levels cannot be used to differentiate restrictive cardiomyopathy from CP.

Topics: Adolescent; Adult; Aged; Biomarkers; Case-Control Studies; Echocardiography, Doppler; Endomyocardial Fibrosis; Female; Heart Failure, Diastolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pericarditis, Constrictive; Prospective Studies; Syndrome; Young Adult

In this study we analyzed putative biomarkers for myocardial remodeling in plasma from 55 endstage heart failure patients with the need for mechanical circulatory support (MCS). We compared our data to 40 healthy controls and examined if MCS by either ventricular assist devices or total artificial hearts has an impact on plasma concentrations of remodeling biomarkers.. Plasma biomarkers were analysed pre and 30 days post implantation of a MCS device using commercially available enzyme linked immunosorbent assays (ELISA). We observed that the plasma concentrations of remodeling biomarkers: tissue inhibitor of metalloproteinase 1 (TIMP1), tenascin C (TNC), galectin 3 (LGALS3), osteopontin (OPN) and of neurohumoral biomarker brain natriuretic peptide (BNP), are significantly elevated in patients with terminal heart failure compared to healthy controls. We did not find elevated plasma concentrations for matrix metalloproteinase 2 (MMP2) and procollagen I C-terminal peptide (PCIP). However, only BNP plasma levels were reduced by MCS, whereas the concentrations of remodeling biomarkers remained elevated or even increased further 30 days after MCS. LGALS3 plasma concentrations at device implantation were significantly higher in patients who did not survive MCS due to multi organ failure (MOF).. Our findings indicate that mechanical unloading in endstage heart failure is not reflected by a rapid reduction of remodeling plasma biomarkers.

Topics: Adolescent; Adult; Aged; Biomarkers; Case-Control Studies; Endomyocardial Fibrosis; Enzyme-Linked Immunosorbent Assay; Female; Galectin 3; Heart Failure; Heart-Assist Devices; Humans; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Osteopontin; Severity of Illness Index; Tenascin; Ventricular Remodeling

Excessive fibrosis contributes to an increase in left ventricular stiffness. The goal of the present study was to investigate the role of connective tissue growth factor (CCN2/CTGF), a profibrotic cytokine of the CCN (Cyr61, CTGF, and Nov) family, and its functional interactions with brain natriuretic peptide (BNP), an antifibrotic peptide, in the development of myocardial fibrosis and diastolic heart failure. Histological examination on endomyocardial biopsy samples from patients without systolic dysfunction revealed that the abundance of CTGF-immunopositive cardiac myocytes was correlated with the excessive interstitial fibrosis and a clinical history of acute pulmonary congestion. In a rat pressure overload cardiac hypertrophy model, CTGF mRNA levels and BNP mRNA were increased in proportion to one another in the myocardium. Interestingly, relative abundance of mRNA for CTGF compared with BNP was positively correlated with diastolic dysfunction, myocardial fibrosis area, and procollagen type 1 mRNA expression. Investigation with conditioned medium and subsequent neutralization experiments using primary cultured cells demonstrated that CTGF secreted by cardiac myocytes induced collagen production in cardiac fibroblasts. Further, G protein-coupled receptor ligands induced expression of the CTGF and BNP genes in cardiac myocytes, whereas aldosterone and transforming growth factor-beta preferentially induced expression of the CTGF gene. Finally, exogenous BNP prevented the production of CTGF in cardiac myocytes. These data suggest that a disproportionate increase in CTGF relative to BNP in cardiac myocytes plays a central role in the induction of excessive myocardial fibrosis and diastolic heart failure.

Topics: Aged; Animals; Cardiomegaly; Cells, Cultured; Connective Tissue Growth Factor; Elasticity; Endomyocardial Fibrosis; Fibrosis; Gene Expression; Humans; Immediate-Early Proteins; Intercellular Signaling Peptides and Proteins; Male; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Nephroblastoma Overexpressed Protein; Rats; Rats, Wistar; RNA, Messenger; Stimulation, Chemical; Stroke Volume; Transcription, Genetic; Ventricular Dysfunction

Myofibrillogenesis regulator-1 (MR-1) augments cardiomyocytes hypertrophy induced by angiotensin II (Ang II) in vitro. However, its roles in cardiac hypertrophy in vivo remain unknown. Here, we investigate whether MR-1 can promote cardiac hypertrophy induced by Ang II in vivo and elucidate the molecular mechanisms of MR-1 on cardiac hypertrophy. We used a model of Ang II-induced cardiac hypertrophy by infusion of Ang II in female mice. In wild-type mice subjected to the Ang II infusion, cardiac hypertrophy developed after 2 weeks. In mice overexpressing human MR-1 (transgenic), however, cardiac hypertrophy was significantly greater than in wild-type mice as estimated by heart weight:body weight ratio, cardiomyocyte area, and echocardiographic measurements, as well as cardiac atrial natriuretic peptide and B-type natriuretic peptide mRNA and protein levels. Our further results showed that cardiac inflammation and fibrosis observed in wild-type Ang II mice were augmented in transgenic Ang II mice. Importantly, increased nuclear factor kappaB activation was significantly increased higher in transgenic mice compared with wild-type mice after 2 weeks of Ang II infusion. In vitro experiments also revealed that overexpression of MR-1 enhanced Ang II-induced nuclear factor kappaB activation, whereas downregulation of MR-1 blocked it in cardiac myocytes. In conclusion, our results suggest that MR-1 plays an aggravative role in the development of cardiac hypertrophy via activation of the nuclear factor kappaB signaling pathway.

Topics: Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomegaly; Endomyocardial Fibrosis; Female; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Muscle Proteins; Myocardium; Natriuretic Peptide, Brain; NF-kappa B; RNA, Messenger; Signal Transduction; Vasoconstrictor Agents; Ventricular Remodeling

Increased cardiac insulin-like growth factor (IGF)-I production is associated with physiological cardiac hypertrophy in athletes, and IGF-I has been recognized as a cardioprotective agent in experimental animal studies. On the other hand, acromegaly which is characterized by an excess of IGF-I has been linked to impaired cardiac function.. Both the relationship between the serum levels of IGF-I and brain natriuretic peptide (BNP), which is released from the cardiac ventricles in response to ventricular stress, and that between IGF-I and the concentrations of the plasma amino-terminal propeptide of procollagen type III (P-III-P), which is associated with myocardial fibrosis, were evaluated in 19 patients after surgical treatment for acromegaly. Echocardiography revealed that left ventricular systolic function and dimensions were within normal range in all patients. Significant inverse correlations were found between IGF-I and the BNP (r=-0.5, p=0.02) and P-III-P levels (r=-0.62, p=0.005).. We observed an inverse significant relationship between IGF-I and both the BNP and P-III-P value in surgically treated acromegaly patients. These observations suggest that appropriate levels of IGF-I have beneficial cardioprotective effects after surgery in patients with acromegaly.

Topics: Acromegaly; Cardiotonic Agents; Endomyocardial Fibrosis; Female; Heart Ventricles; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prospective Studies; Ventricular Function, Left

In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP-/- mice). We observed focal fibrotic lesions in ventricles from BNP-/- mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-beta3, and pro-alpha1(I) collagen [Col alpha1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP-/- mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP-/- mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP-/- mice examined, accompanied by further increase of mRNA expression of TGF-beta3 and Col alpha1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.

Topics: Alleles; Animals; Aorta, Abdominal; Blood Pressure; Blood Volume; Blotting, Northern; Endomyocardial Fibrosis; Heart; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; RNA, Messenger; Transforming Growth Factor beta; Transforming Growth Factor beta3