Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction.

The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell-matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (ECM). This study investigated whether SPARC functions in infarct healing and ECM maturation after myocardial infarction (MI). In comparison with wild-type (WT) mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase in mortality that resulted from an increased incidence of cardiac rupture and failure after MI.

miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling.

The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosis. Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target. Regulation of CTGF expression at the promoter level has been studied extensively, but it is unknown how CTGF transcripts are regulated at the posttranscriptional level.

The detection of temporally defined objects does not require focused attention.

Perceptual grouping is crucial to distinguish objects from their background. Recent studies have shown that observers can detect an object that does not have any unique qualities other than unique temporal properties. A crucial question is whether focused attention is needed for this type of grouping.

Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling.

Background: Dicer, an RNAse III endonuclease critical for processing of pre-microRNAs (miRNAs) into mature 22-nucleotide miRNAs, has proven a useful target to dissect the significance of miRNAs biogenesis in mammalian biology.

Methods And Results: To circumvent the embryonic lethality associated with germline null mutations for Dicer, we triggered conditional Dicer loss through the use of a tamoxifen-inducible Cre recombinase in the postnatal murine myocardium. Targeted Dicer deletion in 3-week-old mice provoked premature death within 1 week accompanied by mild ventricular remodeling and dramatic atrial enlargement.

Reversible isolated left ventricular non-compaction?

Isolated left ventricular non-compaction (LVNC), also known as left ventricular hypertrabeculation, is characterized by the presence of extensive myocardial trabeculation and deep intertrabecular recesses that communicate with the left ventricular cavity. It potentially leads to progressive cardiac failure, thromboembolism, and malignant cardiac arrhythmias. We describe a case of a heart failure patient with diagnostic criteria of LVNC that became less clear after standard heart failure treatment.

The diagnostic value of serum and urinary NT-proBNP for heart failure.

Background: Serum B-type natriuretic peptide (BNP) and the amino-terminal cleavage product of the prohormone (NT-proBNP) have been shown to be valuable parameters for the diagnosis of heart failure (HF) in the general population. Urinary BNP and NT-proBNP have also been suggested for diagnosis of HF. The present study investigated the diagnostic value of both serum and urinary NT-proBNP in selected groups of controls and patients diagnosed with HF.

Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.

Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM.

Population genetic data for 15 STR loci (Identifiler kit) in Honduras.

Allele frequencies for 15 STR autosomal loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818 and FGA) were obtained from a sample of 198 unrelated individuals from Honduras, Central America.

Selecting from dynamic environments: attention distinguishes between blinking and moving.

Pinto, Olivers, and Theeuwes (2006) showed that a static target can be efficiently found among different types of dynamically changing distractors. They hypothesized that attention employs a broad division between static and dynamic information, a hypothesis that conforms with earlier research. In the present study, we investigated whether attention can only make use of this crude division or can exploit more subtle discriminations within the dynamic domain.

Amino-terminal pro-B-type natriuretic peptide testing in renal disease.

Concentrations of amino-terminal pro-B-type natriuretic peptides (NT-proBNP) are typically higher in patients with chronic kidney disease (CKD) than in those without CKD. These elevated levels of NT-proBNP in patients with CKD do not simply reflect the reduced clearance of the peptide; rather, they largely reflect a true-positive finding, identifying the presence of heart disease in these patients, while similarly indicating prognosis as well. Although modestly stronger inverse correlations exist between renal function and NT-proBNP compared with B-type natriuretic peptide (BNP), the dependence of both peptides on renal clearance is similar.

Importance and interpretation of intermediate (gray zone) amino-terminal pro-B-type natriuretic peptide concentrations.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) values between the cut point of 300 ng/L for "ruling out" acute heart failure (HF) and the consensus-recommended age-adjusted cut points for "ruling in" acute HF are referred to as intermediate or gray zone values, which may be seen in approximately 20% of patients with dyspnea in the emergency department. Knowledge of the differential diagnosis of the causes of a gray zone NT-proBNP finding is useful to ascertain the correct diagnosis. Possible causes include cardiac ischemia, atrial fibrillation, and infectious/inflammatory pulmonary diseases.

Severe myocardial fibrosis caused by a deletion of the 5' end of the lamin A/C gene.

Objectives: The goal of this study was to identify the underlying gene defect in a family with inherited myocardial fibrosis.

Background: A large family with an autosomal dominantly inherited form of myocardial fibrosis with a highly malignant clinical outcome has been investigated. Because myocardial fibrosis preceded the clinical and echocardiographic signs, we consider the disease to be a hereditary form of cardiac fibrosis.

Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy.

The intercalated disc (ID) of cardiac myocytes is emerging as a crucial structure in the heart. Loss of ID proteins like N-cadherin causes lethal cardiac abnormalities, and mutations in ID proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein 2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium.

Hemoglobin and N-terminal pro-brain natriuretic peptide: Independent and synergistic predictors of mortality in patients with acute heart failure Results from the International Collaborative of NT-proBNP (ICON) Study.

Background: Hemoglobin and amino-terminal pro-brain natriuretic peptide (NT-proBNP) are both independent predictors of mortality in patients with chronic HF. Their combined predictive power for mortality in the setting of acute HF is uncertain.

Methods: In an international prospective cohort design, we evaluated the relationships between hemoglobin, NT-proBNP, and 60-day mortality in 690 patients with acute HF.

Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.

Cardiac hypertrophy is a common response to injury and hemodynamic stress and an important harbinger of heart failure and death. Herein, we identify the Kruppel-like factor 15 (KLF15) as an inhibitor of cardiac hypertrophy. Myocardial expression of KLF15 is reduced in rodent models of hypertrophy and in biopsy samples from patients with pressure-overload induced by chronic valvular aortic stenosis.

Profiling of the renal kinome: a novel tool to identify protein kinases involved in angiotensin II-dependent hypertensive renal damage.

Regulation of protein kinase activities is crucial in both physiology and disease, but analysis is hampered by the multitude and complexity of kinase networks. We used novel peptide array chips containing 1,152 known kinase substrate sequences to profile different kinase activities in renal lysates from homozygous Ren2 rats, a model characterized by hypertension and angiotensin II (ANG II)-mediated renal fibrosis, compared with Sprague-Dawley (SD) control rats and Ren2 rats treated with an angiotensin-converting enzyme inhibitor (ACEi). Five-wk-old homozygous Ren2 rats were left untreated or treated with the ACEi ramipril (1 mg.

Effect of body mass index on diagnostic and prognostic usefulness of amino-terminal pro-brain natriuretic peptide in patients with acute dyspnea.

Background: Amino (N)-terminal pro-brain natriuretic peptide (NT-proBNP) testing is useful for diagnostic and prognostic evaluation in patients with dyspnea. An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described.

Methods: One thousand one hundred three patients presenting to the emergency department with acute dyspnea underwent analysis.

Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction.

Background: The cell-associated proteoglycan syndecan-1 (Synd1) closely regulates inflammation and cell-matrix interactions during wound healing and tumorigenesis. The present study investigated whether Synd1 may also regulate cardiac inflammation, matrix remodeling, and function after myocardial infarction (MI).

Methods And Results: First, we showed increased protein and mRNA expression of Synd1 from 24 hours on, reaching its maximum at 7 days after MI and declining thereafter.

Structural abnormalities of the inferoseptal left ventricular wall detected by cardiac magnetic resonance imaging in carriers of hypertrophic cardiomyopathy mutations.

Objectives: The purpose of this study was to evaluate whether structural left ventricular (LV) abnormalities can be observed in hypertrophic cardiomyopathy (HCM) mutation carriers who have not yet developed echocardiographic signs of hypertrophy by using cardiac magnetic resonance imaging (CMR).

Background: Hypertrophic cardiomyopathy is caused by mutations of genes encoding for sarcomeric proteins. Myocyte disarray and interstitial fibrosis precede the development of regional hypertrophy in HCM mutation carriers (carriers).