Notch and retinoic acid signals regulate macrophage formation from endocardium downstream of Nkx2-5.

Hematopoietic progenitors are enriched in the endocardial cushion and contribute, in a Nkx2-5-dependent manner, to tissue macrophages required for the remodeling of cardiac valves and septa. However, little is known about the molecular mechanism of endocardial-hematopoietic transition. In the current study, we identified the regulatory network of endocardial hematopoiesis.

Urinary titin is not an early biomarker of skeletal muscle atrophy induced by muscle denervation in mice.

Early detection of skeletal muscle atrophy is important to prevent further muscle weakness. However, there are few non-invasive biomarkers for skeletal muscle atrophy. Recent studies have reported that the N-terminal fragment (N-titin) of titin, a giant sarcomeric protein, is detected in the urine of patients with muscle damage.

Evaluation of Ductal Tissue in Coarctation of the Aorta Using X-Ray Phase-Contrast Tomography.

We assessed the histological accuracy of X-ray phase-contrast tomography (XPCT) and investigated three-dimensional (3D) ductal tissue distribution in coarctation of the aorta (CoA) specimens. We used nine CoA samples, including the aortic isthmus, ductus arteriosus (DA), and their confluences. 3D images were obtained using XPCT.

Thiamine treatment preserves cardiac function against ischemia injury via maintaining mitochondrial size and ATP levels.

Thiamine (vitamin B1) is necessary for energy production, especially in the heart. Recent studies have demonstrated that thiamine supplementation for cardiac diseases is beneficial. However, the detailed mechanisms underlying thiamine-preserved cardiac function have not been elucidated.

p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart.

In the mammalian heart, the left ventricle (LV) rapidly becomes more dominant in size and function over the right ventricle (RV) after birth. The molecular regulators responsible for this chamber-specific differential growth are largely unknown. We found that cardiomyocytes in the neonatal mouse RV had lower proliferation, more apoptosis, and a smaller average size compared with the LV.

Troponin T amino acid mutation (ΔK210) knock-in mice as a neonatal dilated cardiomyopathy model.

Background: Dilated cardiomyopathy (DCM) in children is often associated with poor morbidity and mortality and exhibits distinct pathological entities from those of adult DCM. Owing to the limited number of patients and the lack of a good animal model, the molecular mechanisms underlying pediatric DCM remain poorly understood. The purpose of this study is to establish an animal model of neonatal DCM and identify early progression factors.

Pathophysiologic Role of Molecules Determining Arteriovenous Differentiation in Adult Life.

The structural differences between arteries and veins are genetically predetermined. Vascular identity markers, the molecular markers specific to veins and arteries, determine the differential development of vessels during embryogenesis and their expression persists in adult vessels. It is revealed that they can be reactivated under various pathophysiologic conditions even after vessel differentiation.

Fibrosis growth factor 23 is a promoting factor for cardiac fibrosis in the presence of transforming growth factor-β1.

Myocardial fibrosis is often associated with cardiac hypertrophy; indeed, fibrosis is one of the most critical factors affecting prognosis. We aimed to identify the molecules involved in promoting fibrosis under hypertrophic stimuli. We previously established a rat model of cardiac hypertrophy by pulmonary artery banding, in which approximately half of the animals developed fibrosis in the right ventricle.

Effect of Long-term Administration of Prostaglandin E on Morphologic Changes in Ductus Arteriosus.

Background: To improve survival of patients with hypoplastic left heart syndrome, combination therapy with bilateral pulmonary artery banding and prostaglandin E (PGE)-mediated ductal patency was developed as an alternative for high-risk neonates in Japan. However, the effect of long-term PGE administration on ductus arteriosus remains unclear. Synchrotron radiation-based X-ray phase-contrast tomography (XPCT) enables clear visualization of soft tissues at an approximate spatial resolution of 12.

Standard-dose gentamicin does not increase risk of patent ductus arteriosus.

Background: Rates of patent ductus arteriosus (PDA) and infection are high in preterm infants. Preterm infants with infection are more likely to develop symptomatic PDA, a potentially fatal disease. Clinically, gentamicin is widely used for early-onset infection in neonates including preterm infants.

Transcriptional profiles in the chicken ductus arteriosus during hatching.

The ductus arteriosus, an essential embryonic blood vessel between the pulmonary artery and the descending aorta, constricts after birth or hatching and eventually closes to terminate embryonic circulation. Chicken embryos have two long ductus arteriosi, which anatomically differ from mammal ductus arteriosus. Each long ductus arteriosus is divided into two parts: the pulmonary artery-sided and descending aorta-sided ductus arteriosi.

Urinary Titin Is Increased in Patients After Cardiac Surgery.

Few non-invasive biomarkers have been used to detect myocardial injury in patients with heart diseases. Recently, the N-terminal fragment (N-titin) of titin, a giant sarcomeric protein, which is involved in muscular passive tension and viscoelasticity, has been reported to detect muscle damage in patients with cardiomyopathy as well as in patients with skeletal muscle dystrophy and in healthy volunteers with endurance exercise. In the present study, we evaluated whether urinary N-titin is changed during a perioperative period and whether its increase reflects myocardial damage.

Left Atrial Stenosis Induced Pulmonary Venous Arterialization and Group 2 Pulmonary Hypertension in Rat.

The mechanism of mitral stenosis-induced pulmonary venous arterialization and group 2 pulmonary hypertension (PH) is unclear. There is no rodent model of group 2 PH, due to mitral stenosis (MS), to facilitate the investigation of disease mechanisms and potential therapeutic strategies. We present a novel rat model of pulmonary venous congestion-induced pulmonary venous arterialization and group 2 PH caused by left atrial stenosis (LAS).

Prostaglandin E Receptor EP4 Inhibition Contracts Rat Ductus Arteriosus.

Background: Patent ductus arteriosus (PDA) is common in premature infants. Cyclooxygenase inhibitors such as indomethacin, which inhibit prostaglandin E(PGE) synthesis, are currently the sole treatments for patients with PDA. Their efficacy are, however, frequently limited, and adverse effects are problematic.

Pyruvate dehydrogenase activation precedes the down-regulation of fatty acid oxidation in monocrotaline-induced myocardial toxicity in mice.

Fatty acid (FA) oxidation is impaired and glycolysis is promoted in the damaged heart. However, the factor(s) in the early stages of myocardial metabolic impairment remain(s) unclear. C57B6 mice were subcutaneously administered monocrotaline (MCT) in doses of 0.

Truncated dystrophin ameliorates the dystrophic phenotype of mdx mice by reducing sarcolipin-mediated SERCA inhibition.

Duchenne muscular dystrophy (DMD) and the less severe Becker muscular dystrophy (BMD) are due to mutations in the DMD gene. Previous reports show that in-frame deletion of exons 45-55 produces an internally shorted, but functional, dystrophin protein resulting in a very mild BMD phenotype. In order to elucidate the molecular mechanism leading to this phenotype, we generated exon 45-55 deleted dystrophin transgenic/mdx (Tg/mdx) mice.

CCN3 secreted by prostaglandin E inhibits intimal cushion formation in the rat ductus arteriosus.

The ductus arteriosus (DA), an essential fetal shunt between the pulmonary trunk and the descending aorta, changes its structure during development. Our previous studies have demonstrated that prostaglandin E (PGE)-EP4 signaling promotes intimal cushion formation (ICF) by activating the migration of DA smooth muscle cells via the secretion of hyaluronan. We hypothesized that, in addition to hyaluronan, PGE may secrete other proteins that also regulate vascular remodeling in the DA.

The serine/threonine-protein kinase/endoribonuclease IRE1α protects the heart against pressure overload-induced heart failure.

Heart failure is associated with induction of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). The serine/threonine protein kinase/endoribonuclease IRE1α is a key protein in ER stress signal transduction. IRE1α activity can induce both protective UPR and apoptotic downstream signaling events, but the specific role for IRE1α activity in the heart is unknown.

Distinct Vascular Remodeling Pattern of Adult Rats with Carotid-Jugular Shunt.

Background: Previous research has revealed that patent vein grafts lose their venous identity Eph-B4 but do not gain arterial identity ephrin-B2 during adaptation to the arterial circulation, and vascular identity marker, for example, the Eph-B4 signaling is a critical determinant of venous wall thickness of vein grafts. But what is the remodeling pattern, especially the remodeling pattern of vascular identity in the venous segment of arteriovenous shunt at a late stage postoperation has not been fully explored. This study was conducted to characterize the remodeling pattern of shear stress, vascular identity, structural composition and morphology, and transcriptional profiles in jugular segment of carotid-jugular (CJ) shunt and/or pulmonary artery (PA), which delivers an increased amount of mixed blood at a late stage postoperation in adult rats.

A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evidence at molecular, cellular and whole heart levels to implicate a sarcolemma membrane targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase.

Time-dependent effects of ipragliflozin on behaviour and energy homeostasis in normal and type 2 diabetic rats: continuous glucose telemetry analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote urinary glucose excretion. Conversely, they cause behavioural changes, such as hyperphagia, that result in a positive energy balance. The relationship between energy homeostasis and SGLT2 inhibitors-induced behavioural changes remains unclear.

The effects of heat stress on morphological properties and intracellular signaling of denervated and intact soleus muscles in rats.

The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth-related hypertrophy in sham-operated muscles and attenuated atrophy in denervated muscles.

Pulmonary hypertension due to left heart disease causes intrapulmonary venous arterialization in rats.

Objective: A rat model of left atrial stenosis-associated pulmonary hypertension due to left heart diseases was prepared to elucidate its mechanism.

Methods: Five-week-old Sprague-Dawley rats were randomly divided into 2 groups: left atrial stenosis and sham-operated control. Echocardiography was performed 2, 4, 6, and 10 weeks after surgery, and cardiac catheterization and organ excision were subsequently performed at 10 weeks after surgery.

Cardiac myocyte p38α kinase regulates angiogenesis via myocyte-endothelial cell cross-talk during stress-induced remodeling in the heart.

Stress-induced p38 mitogen-activated protein kinase (MAPK) activity is implicated in pathological remodeling in the heart. For example, constitutive p38 MAPK activation in cardiomyocytes induces pathological features, including myocyte hypertrophy, apoptosis, contractile dysfunction, and fetal gene expression. However, the physiological function of cardiomyocyte p38 MAPK activity in beneficial compensatory vascular remodeling is unclear.