Beta blockers prevent correlation of plasma ACE2 activity with echocardiographic parameters in patients with idiopathic dilated cardiomyopathy.

Plasma angiotensin-converting enzyme (ACE) 2 activity has been demonstrated to be an independent prognostic marker in Chagas' disease, equally potent as B-type natriuretic peptide. This study aimed to investigate the prognostic potency of circulating ACE2 activity in patients with idiopathic dilated cardiomyopathy (DCM). Blood samples were withdrawn from patients with idiopathic DCM and healthy control subjects.

Prognostic value of circulating levels of stem cell growth factor beta (SCGF beta) in patients with Chagas' disease and idiopathic dilated cardiomyopathy.

Chagas' disease (CD) often leads to dilated cardiomyopathy (DCM), and during its chronic stage hematopoietic stem or progenitor cells are involved in its pathological process. However, it is not clear whether stem cell growth factor (SCGF) beta can be regulated in patients with CD and idiopathic DCM. In present study, we aim to investigate the plasma SCGF beta concentration and its correlation with echocardiographic parameters and clinical outcome.

The genetic deletion of Mas abolishes salt induced hypertension in mice.

The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor and is associated with angiotensin-(1-7) signaling. We investigated the effect of Mas-deficiency on blood pressure regulation under physiological conditions and salt load using radiotelemetry. Mas-knockout mice and their wild-type controls received a telemetry implant in the carotid artery.

Prognostic significance of circulating levels of hepatocyte growth factor in patients with chagas' disease and idiopathic dilated cardiomyopathy.

Objectives: Hepatocyte growth factor (HGF) plays an important role in the improvement in cardiac function and remodeling in a variety of cardiovascular diseases. It is also a strong predictor of mortality in some heart failure (HF) patients. However, its prognostic value in patients with Chagas' disease (CD) or idiopathic dilated cardiomyopathy (DCM) remains to be investigated.

Does the aminopeptidase A have prognostic and diagnostic value in Chagas disease and other dilated cardiomyopathies?

Chagas disease (CD), which is caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. We investigated if plasma activity of one of the enzymes being part of the renin-angiotensin system, aminopeptidase A (APA), has diagnostic and prognostic potency in patients with CD and dilated cardiomyopathies (DCMs) due to other causes. Blood samples were taken from 94 patients with CD, 46 patients with DCM, and 34 healthy control subjects.

Plasma ACE2 activity is an independent prognostic marker in Chagas' disease and equally potent as BNP.

Background: Angiotensin-converting enzyme (ACE) 2 is a novel homologue of ACE. It metabolizes angiotensin (Ang)II to Ang-(1-7). This study aims to investigate the diagnostic and prognostic potency of circulating ACE2 activity in patients with heart failure (HF) from Chagas' disease (CD).

Amino-terminal fragment of C-type natriuretic peptide precursor and C-type natriuretic peptide do not correlate in patients with Chagas disease: role for neutral endopeptidase.

Atrial and B-type natriuretic peptides (ANP and BNP), but not C-type natriuretic peptide (CNP), have been identified to be diagnostic and prognostic markers in Chagas disease (CD). Although ANP and BNP excessively rise in patients with CD, increase in CNP is just minor. Our study aimed to investigate the mechanisms leading to CNP insensitivity to heart failure (HF) stimuli.

Cardiac phenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts.

Aims: Our aim was to determine the contribution of the three angiotensin (Ang) II receptor subtypes (AT(1a), AT(1b), AT(2)) to coronary responsiveness, cardiac histopathology, and tissue Ang II levels using mice deficient for one, two, or all three Ang II receptors.

Methods And Results: Hearts of knockout mice and their wild-type controls were collected for histochemistry or perfused according to Langendorff, and kidneys were removed to measure tissue Ang II. Ang II dose-dependently decreased coronary flow (CF) and left ventricular systolic pressure (LVSP), and these effects were absent in all genotypes deficient for AT(1a), independently of AT(1b) and AT(2).

Candidate Agtr2 influenced genes and pathways identified by expression profiling in the developing brain of Agtr2(-/y) mice.

Intellectual disability (ID) is a common developmental disability observed in 1 to 3% of the human population. A possible role for the Angiotensin II type 2 receptor (AGTR2) in brain function, affecting learning, memory, and behavior, has been suggested in humans and rodents. Mice lacking the Agtr2 gene (Agtr2(-/y)) showed significant impairment in their spatial memory and exhibited abnormal dendritic spine morphology.

Angiotensin-(1-7) and the g protein-coupled receptor MAS are key players in renal inflammation.

Angiotensin (Ang) II mediates pathophysiologial changes in the kidney. Ang-(1-7) by interacting with the G protein-coupled receptor Mas may also have important biological activities.In this study, renal deficiency for Mas diminished renal damage in models of renal insufficiency as unilateral ureteral obstruction and ischemia/reperfusion injury while the infusion of Ang-(1-7) to wild-type mice pronounced the pathological outcome by aggravating the inflammatory response.

Prognostic value of natriuretic peptides in Chagas' disease: a head-to-head comparison of the 3 natriuretic peptides.

To determine the diagnostic and prognostic value of natriuretic peptides in patients with Chagas' disease (CD), the authors first measured atrial (ANP), B-type (BNP), and C-type natriuretic peptide (CNP) and compared their diagnostic and prognostic capacity with that in other dilated cardiomyopathies (DCM). The CD and DCM patients were subdivided according to their New York Heart Association (NYHA) classification. Circulating ANP and more pronounced BNP, but not CNP, were increased in CD and DCM patients in relation to NYHA class.

Angiotensin-(1-7) stimulates hematopoietic progenitor cells in vitro and in vivo.

Effects of angiotensin (Ang)-(1-7), an AngII metabolite, on bone marrow-derived hematopoietic cells were studied. We identified Ang-(1-7) to stimulate proliferation of human CD34(+) and mononuclear cells in vitro. Under in vivo conditions, we monitored proliferation and differentiation of human cord blood mononuclear cells in NOD/SCID mice.

The angiotensin-(1-7) receptor agonist AVE0991 is cardioprotective in diabetic rats.

Angiotensin-(1-7) is associated with beneficial effects in cardiovascular diseases. In this study, we determined the effect of AVE0991, a nonpeptide angiotensin-(1-7) receptor agonist, on cardiac function in an animal model of diabetes mellitus type I. Diabetes was induced in Sprague-Dawley rats by a single injection of streptozotocin (70 mg/kg).

Cardiovascular phenotype of mice lacking all three subtypes of angiotensin II receptors.

Angiotensin II activates two distinct receptors, the angiotensin II receptors type 1 (AT(1)) and type 2 (AT(2)). In rodents, two AT(1) subtypes were identified (AT(1a) and AT(1b)). To determine receptor-specific functions and possible angiotensin II effects independent of its three known receptors we generated mice deficient in either one of the angiotensin II receptors, in two, or in all three (triple knockouts).

Prognostic value of natriuretic peptides in Chagas' disease: a 3-year follow-up investigation.

Background: Chagas' disease (CD) affects around 18 million people in Latin America. To determine the diagnostic and prognostic value of natriuretic peptides in patients with CD, we measured atrial (ANP) and brain natriuretic peptide (BNP), and compared the findings with other dilated cardiomyopathies (DCM).

Methods: Blood samples were obtained from 111 CD patients, 62 patients with DCM due to other causes, and 43 gender- and age-matched healthy subjects.

Endothelial dysfunction through genetic deletion or inhibition of the G protein-coupled receptor Mas: a new target to improve endothelial function.

Background: Endothelial dysfunction is an initial step in the pathogenesis of cardiovascular diseases. Since we previously identified the G protein-coupled receptor Mas as a receptor for angiotensin (Ang)-(1-7), a heptapeptide with endothelium-dependent vasorelaxant properties, we investigated whether alterations on the Ang-(1-7)/Mas axis alter endothelial function.

Results: Ang-(1-7)-mediated relaxation of murine wild-type mesenteric arteries was equally impaired in both wild-type arteries pretreated with the Ang-(1-7) receptor blocker, A779, and arteries isolated from Mas-deficient mice.

Accelerated mitochondrial adenosine diphosphate/adenosine triphosphate transport improves hypertension-induced heart disease.

Background: Strong evidence suggests that mitochondrial malfunction, which leads to disturbed energy metabolism and stimulated apoptosis, is a linchpin in the induction and manifestation of cardiac failure. An adequate exchange of ATP and ADP over the inner mitochondrial membrane by the adenine nucleotide translocase (ANT) is thereby essential to guarantee the cellular energy supply.

Methods And Results: To explore the effect of an ameliorated mitochondrial ATP/ADP transportation on cardiac dysfunction, we generated transgenic rats overexpressing ANT1 in the heart (ANT rats) and crossed them with renin-overexpressing rats (REN rats) suffering from hypertension-induced cardiac insufficiency.

Does the C-type natriuretic peptide have prognostic value in chagas disease and other dilated cardiomyopathies?

Atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP) are powerful neurohormonal indicators of left-ventricular function and prognosis in heart failure (HF). Chagas disease (CD) caused by the protozoan Trypanosoma cruzi remains a major cause of HF in Latin America. We assessed whether the plasma concentration of the third natriuretic peptide, C-type natriuretic peptide (CNP), also has diagnostic and prognostic properties in patients with CD or other dilated cardiomyopathies (DCM).

G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor.

Background: We previously identified the G-protein-coupled receptor Mas, encoded by the Mas proto-oncogene, as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. We therefore tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT1.

Methods And Results: In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT1 receptor-mediated, angiotensin II-induced production of inositol phosphates and mobilization of intracellular Ca2+ was diminished by 50% after coexpression of Mas, despite a concomitant increase in angiotensin II binding capacity.

Angiotensin deficiency in mice leads to dilated cardiomyopathy.

To explore the role of angiotensin II, we assessed hemodynamics and cardiac function in angiotensinogen-deficient mice in comparison to wild-type animals. Left ventricular end-diastolic diameter and wall thickness were evaluated by echocardiography and systolic and diastolic left ventricular function by pressure-volume relations using a micro-conductance catheter. Compared to wild-type animals, the angiotensinogen-deficient mice were hypotensive and showed impaired systolic function.

Fibrosis rather than blood pressure determines cardiac BNP expression in mice.

Background: Since first reports demonstrated interactions between the natriuretic peptide (NPS) and renin-angiotensin system (RAS), our experiments should clarify whether cardiac brain natriuretic peptide (BNP) is regulated in mice genetically altered for components of the RAS.

Methods And Results: The study was carried out in hypotensive AT1- and angiotensinogen (ANG)-, and normotensive AT2-knockout mice, and in hypertensive animals overexpressing ANG and wildtype controls of each genotype. Ventricular BNP expression was analyzed by RNase-protection assay (RPA) (n=6).

Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas.

The renin-angiotensin system plays a critical role in blood pressure control and body fluid and electrolyte homeostasis. Besides angiotensin (Ang) II, other Ang peptides, such as Ang III [Ang-(2-8)], Ang IV [Ang-(3-8)], and Ang-(1-7) may also have important biological activities. Ang-(1-7) has become an angiotensin of interest in the past few years, because its cardiovascular and baroreflex actions counteract those of Ang II.