Cytokine therapy prevents left ventricular remodeling and dysfunction after myocardial infarction through neovascularization.

Pretreatment with a combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) has been reported to attenuate left ventricular (LV) remodeling after acute myocardial infarction (MI). We here examined whether the cytokine treatment started after MI has also beneficial effects. Anterior MI was created in the recipient mice whose bone marrow had been replaced with that of transgenic mice expressing enhanced green fluorescent protein (GFP).

A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5.

The cardiac homeobox transcription factor CSX/NKX2-5 plays an important role in vertebrate heart development. Using a yeast two-hybrid screening, we identified a novel LIM domain-containing protein, named CSX-associated LIM protein (Cal), that interacts with CSX/NKX2-5. CSX/NKX2-5 and Cal associate with each other both in vivo and in vitro, and the LIM domains of Cal and the homeodomain of CSX/NKX2-5 were necessary for mutual binding.

Direct measurement of Ca2+ concentration in the SR of living cardiac myocytes.

Although abnormal sarcoplasmic reticulum (SR) Ca(2+) handling may cause heart failure, there has been no method to directly measure Ca(2+) concentration in SR ([Ca(2+)](SR)) of living cardiomyocytes. We have measured [Ca(2+)](SR) by expressing novel fluorescent Ca(2+) indicators yellow cameleon (YC) 2.1, YC3er, and YC4er in cultured neonatal rat cardiomyocytes.

Role of Na+-Ca2+ exchanger in myocardial ischemia/reperfusion injury: evaluation using a heterozygous Na+-Ca2+ exchanger knockout mouse model.

We used Na(+)-Ca(2+) exchanger (NCX) knockout mice to evaluate the effects of NCX in cardiac function and the infarct size after ischemia/reperfusion injury. The contractile function in NCX KO mice hearts was significantly better than that in wild type (WT) mice hearts after ischemia/reperfusion and the infarct size was significantly small in NCX KO mice hearts compared with that in WT mice hearts. NCX is critically involved in the development of ischemia/reperfusion-induced myocardial injury and therefore the inhibition of NCX function may contribute to cardioprotection against ischemia/reperfusion injury.

Adult cardiac Sca-1-positive cells differentiate into beating cardiomyocytes.

Although somatic stem cells have been reported to exist in various adult organs, there have been few reports concerning stem cells in the heart. We here demonstrate that Sca-1-positive (Sca-1+) cells in adult hearts have some of the features of stem cells. Sca-1+ cells were isolated from adult murine hearts by a magnetic cell sorting system and cultured on gelatin-coated dishes.

Heat shock transcription factor 1 protects cardiomyocytes from ischemia/reperfusion injury.

Background: Because cardiomyocyte death causes heart failure, it is important to find the molecules that protect cardiomyocytes from death. The death trap is a useful method to identify cell-protective genes.

Methods And Results: In this study, we isolated the heat shock transcription factor 1 (HSF1) as a protective molecule by the death trap method.

Oxidative stress-induced signal transduction pathways in cardiac myocytes: involvement of ROS in heart diseases.

Reactive oxygen species (ROS) are proposed to contribute to the deterioration of cardiac function in patients with heart diseases. It has been reported that ROS are increased in the failing heart and involved in atherosclerosis, myocardial ischemia/reperfusion injury, and heart failure. Antioxidant enzymes are decreased in the decompensated heart, depressing defense mechanisms against oxidative stress.

Leukemia inhibitory factor enhances survival of cardiomyocytes and induces regeneration of myocardium after myocardial infarction.

Background: Myocardial infarction (MI) is a leading cause of cardiac morbidity and mortality in many countries; however, the treatment of MI is still limited.

Methods And Results: We demonstrate a novel gene therapy for MI using leukemia inhibitory factor (LIF) cDNA. We injected LIF plasmid DNA into the thigh muscle of mice immediately after inducing MI.

Roles of cardiac transcription factors in cardiac hypertrophy.

Different cell types, equipped with unique structure and function, synthesize different sets of proteins on the basis of different patterns of gene expression, even though their genomes are identical. Cardiac transcription factors have been reported to control a cardiac gene program and thus to play a crucial role in transcriptional regulation during embryogenesis. Recently, postnatal roles of cardiac transcription factors have been extensively investigated.

Pleiotropic effects of cytokines on acute myocardial infarction: G-CSF as a novel therapy for acute myocardial infarction.

Many cytokines have been reported to be increased in human and animal models with cardiovascular diseases. Myocardial infarction (MI) is accompanied with an inflammatory reaction which induces cardiac dysfunction and remodeling. The inflammatory reaction has been investigated in animal models of MI or myocardial ischemia-reperfusion injury.

Beating is necessary for transdifferentiation of skeletal muscle-derived cells into cardiomyocytes.

Cell transplantation could be a potential therapy for heart damage. Skeletal myoblasts have been expected to be a good cell source for autologous transplantation; however, the safety and efficacy of their transplantation are still controversial. Recent studies have revealed that skeletal muscle possesses the stem cell population that is distinct from myoblasts.

Stretch-modulation of second messengers: effects on cardiomyocyte ion transport.

In cardiomyocytes, mechanical stress induces a variety of hypertrophic responses including an increase in protein synthesis and a reprogramming of gene expression. Recently, the calcium signaling has been reported to play an important role in the development of cardiac hypertrophy. In this article, we report on the role of the calcium signaling in stretch-induced gene expression in cardiomyocytes.

Dual effects of the homeobox transcription factor Csx/Nkx2-5 on cardiomyocytes.

A homeobox-containing transcription factor Csx/Nkx2-5 is an important regulator of cardiac development. Many different human CSX/NKX2-5 mutations have been reported to cause congenital heart disease. We here examined the effects of three representative CSX/NKX2-5 mutations on cardiomyocyte differentiation and death with the use of the P19CL6 cardiomyogenic cell lines.

Inhibitory molecules in signal transduction pathways of cardiac hypertrophy.

Cardiac hypertrophy is induced by a variety of diseases, such as hypertension, valvular diseases, myocardial infarction, and endocrine disorders. Although cardiac hypertrophy may initially be a beneficial response that normalizes wall stress and maintains normal cardiac function, prolonged hypertrophy is a leading cause of heart failure and sudden death. A number of studies have elucidated molecules responsible for the development of cardiac hypertrophy, including the mitogen-activated protein (MAP) kinases pathway, Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and calcium/calmodulin-dependent protein phosphatase calcineurin pathway.

Quantitative analysis of glomerular type IV collagen alpha3-5 chain expression in children with thin basement membrane disease.

Thin basement membrane disease (TBMD) and Alport syndrome, two forms of childhood nephritis, have generally been considered to be hereditary diseases. In Alport syndrome, several reports have demonstrated pathogenic mutations of the genes encoding type IV collagen alpha3, 4 and/or 5 chain [alpha3, 4 and/or 5(IV)]. Previous immunohistochemical studies indicated that these antigens were absent from the glomerular basement membrane (GBM) in Alport syndrome, whilst a normal labeling pattern was maintained in TBMD.

[Shear stress-induced platelet aggregation in children with minimal change nephrotic syndrome].

Analysis of the hemostasis system using biochemical techniques in children with minimal change nephrotic syndrome (MCNS) has previously been restricted to in vitro assays. The recent introduction of measurement of shear stress-induced platelet aggregation (SIPA) using platelet-rich plasma (PRP) has facilitated detailed investigation of the hemostatic system in vivo. In order to further analyze the etiology of the thrombotic tendency exhibited by patients with childhood MCNS, we investigated SIPA at both low shear stress (L-SIPA) and high shear stress (H-SIPA) in 14 children with MCNS using PRP collected weekly after commencing prednisolone therapy.

Molecular and cellular mechanisms of mechanical stress-induced cardiac hypertrophy.

Congestive heart failure is one of the major issues for cardiologists. Since cardiac hypertrophy deteriorates into heart failure, it is important to elucidate the mechanisms of cardiac hypertrophy. Hemodynamic overload, namely mechanical stress, is a major cause for cardiac hypertrophy.

Role of the limbus in femoral-head deformation in developmental dislocation of the hip: findings of two-directional hip arthrography.

Two-directional arthrographic findings made during conservative treatment of developmental dislocation of the hip were compared with the femoral-head configurations and radiological results obtained from long-term follow-up examinations in this retrospective study. Sixty hips were followed until at least age 14. Arthrography was carried out according to Terazawa's method.

Changes of blood flow in the mucosa underlying a mandibular denture following pressure assumed as a result of light clenching.

The aim of this study was to investigate the influence of the continuous compression assumed as a result of light clenching on the blood flow of the denture underlying mucosa in tissue-supported or tooth-tissue-supported denture wearers. Measurements were carried out on eight removable partial denture wearers (three males and five females, from 50 to 72 years, mean age: 61.5 years).

Continuous blockade of L-type Ca2+ channels suppresses activation of calcineurin and development of cardiac hypertrophy in spontaneously hypertensive rats.

We examined whether Ca2+ channel blockers inhibit the activation of the Ca2+-dependent phosphatase calcineurin and the development of cardiac hypertrophy in spontaneously hypertensive rats (SHR). We randomly divided 12-week-old SHR into three groups, one each receiving vehicle, bolus injection or continuous infusion of nifedipine (10 mg/kg/day) from 12 to 24 weeks of age. Systolic blood pressure (BP) and heart rate were measured every week after the treatment using the tail-cuff plethysmography method.

Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart.

Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice. Transgenic mice that overexpress a dominant negative mutant of Csx/Nkx2-5 (DN-TG mice) showed degeneration of cardiac myocytes and impairment of cardiac function.

Sodium calcium exchanger plays a key role in alteration of cardiac function in response to pressure overload.

The Na+-Ca2+ exchanger (NCX) on the plasma membrane is thought to be the main calcium extrusion system from the cytosol to the extracellular space in many mammalian excitable cells, including cardiac myocytes. However, the pathophysiological role of NCX in the heart is still unclear because of the lack of known specific inhibitors of NCX. To determine the role of NCX in cardiac contraction and the development of cardiac hypertrophy, we imposed pressure overload on the heart of heterozygous NCX knockout (KO) mice by constricting transverse aorta, and examined cardiac function and morphology 3 wk after operation.

Integrins play a critical role in mechanical stress-induced p38 MAPK activation.

Mechanical stress activates various hypertrophic responses, including activation of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Stretch activated extracellular signal-regulated kinases partly through secreted humoral growth factors, including angiotensin II, whereas stretch-induced activation of c-Jun NH(2)-terminal kinases and p38 MAPK was independent of angiotensin II. In this study, we examined the role of integrin signaling in stretch-induced activation of p38 MAPK in cardiomyocytes of neonatal rats.