Prostacyclin receptor agonists induce DUSP1 to inhibit pulmonary artery smooth muscle cell proliferation.

Aims: Upregulated p38 signaling is implicated in the accelerated proliferation of pulmonary artery smooth muscle cells (PA-SMCs) and the pathogenesis of pulmonary artery remodeling observed in pulmonary arterial hypertension (PAH). Previously, we reported that after endothelin-1 (ET-1) pretreatment, bone morphogenetic protein 2 (BMP2) activates p38 signaling and accelerates PA-SMC proliferation. The activity of p38 signaling is tightly regulated by the inactivation of dual-specificity phosphatase 1 (DUSP1).

Endothelin-1 alters BMP signaling to promote proliferation of pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is characterized by abnormal outgrowth of pulmonary artery smooth muscle cells (PASMCs) of the media. Abundant expression of endothelin-1 (ET-1) and activated p38 mitogen-activated protein kinase (p38MAPK) has been observed in PAH patients. p38MAPK has been implicated in cell proliferation.

Giant coronary fistula aneurysm presenting as a progressing left-sided asymptomatic mediastinal mass with systolic dominant Doppler flow: a case report.

Background: Cases of giant coronary artery aneurysms (GCAAs) associated with coronary fistula are rarely reported, and they present with various symptoms, including coronary steal syndrome. We report an uncommon case of an asymptomatic giant coronary fistula aneurysm presenting as a progressing left-sided mediastinal mass that has been tracked for years.

Case Summary: A 67-year-old healthy asymptomatic woman was referred to our hospital because of an abnormal shadow on her chest radiography revealing a left-sided mediastinal mass that had progressed in size over the past 4 years.

Administration of β-lactam antibiotics and delivery method correlate with intestinal abundances of Bifidobacteria and Bacteroides in early infancy, in Japan.

The intestinal microbiome changes dynamically in early infancy. Colonisation by Bifidobacterium and Bacteroides and development of intestinal immunity is interconnected. We performed a prospective observational cohort study to determine the influence of antibiotics taken by the mother immediately before delivery on the intestinal microbiome of 130 healthy Japanese infants.

Endothelin-1 induces lysyl oxidase expression in pulmonary artery smooth muscle cells.

The increase in thickening of the arterial wall of pulmonary arterial hypertension (PAH) includes cellular proliferation as well as matrix deposition and interrupted internal elastic lamina (IEL) consisting of a thick homogeneous sheet of elastin. Little is, although, known about the detail of IEL formation in PAH. Endothelin-1 is overexpressed in pulmonary arterioles of PAH.

Successful Liposteroid Therapy for a Recurrent Idiopathic Pulmonary Hemosiderosis with Down Syndrome.

Idiopathic pulmonary hemosiderosis (IPH) is a rare and life-threatening disorder. Early diagnosis and appropriate management are essential for their better prognosis and patients' quality of life (QOL). It is considered that Down syndrome patients with IPH have a worse prognosis compared to other IPH cases.

Maternal antimicrobial use at delivery has a stronger impact than mode of delivery on bifidobacterial colonization in infants: a pilot study.

Objective: To investigate factors related to bifidobacterial colonization in early infancy, with a focus on maternal antimicrobial use at delivery.

Study Design: A cross-sectional pilot study was performed. Feces samples of 33 Japanese healthy infants were collected over 10 months and analyzed by next-generation sequencing to examine the diversity and abundance of the gut microbiota.

Bosentan reverses the hypoxia-induced downregulation of the bone morphogenetic protein signaling in pulmonary artery smooth muscle cells.

Aims: Pulmonary hypertension (PH) is a common complication of chronic hypoxic lung diseases. Bone morphogenetic protein (BMP) and endothelin-1 signaling pathways have been shown to be altered in hypoxic PH and to play crucial roles in the associated pulmonary artery remodeling. We, therefore, aimed to study the potential link between hypoxia and the alteration of BMP and endothelin-1 signaling observed in pulmonary artery smooth muscle cells (PA-SMCs) in hypoxic PH.

Antagonists to endothelin receptor type B promote apoptosis in human pulmonary arterial smooth muscle cells.

Aims: Vascular remodeling results from aberrations in the balance between cell proliferation and death, which is seen in the obstructive vasculature of pulmonary arterial hypertension (PAH). Endothelin (ET)-1 has a potent proliferative activity on vascular smooth muscle cells, and ET receptor inhibitors are used to treat PAH; however, it remains unclear whether ET receptor inhibition contributes to the apoptosis of pulmonary arterial smooth muscle cells (PASMCs), another cause of pulmonary vascular remodeling.

Main Methods: Cultured human PASMCs were treated with the ETA receptor antagonist BQ-123 (100μM), or the ETB antagonist A-192621 (1-100μM) or BQ-788 (1-100μM) for 48h.

Prevention of pulmonary hypoplasia and pulmonary vascular remodeling by antenatal simvastatin treatment in nitrofen-induced congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) has a high mortality rate mainly due to lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). Simvastatin has been shown to prevent the development of pulmonary hypertension (PH) in experimental models of PH. We, therefore, hypothesized that antenatal simvastatin would attenuate PPHN in nitrofen-induced CDH in rats.

Endothelin-Bone morphogenetic protein type 2 receptor interaction induces pulmonary artery smooth muscle cell hyperplasia in pulmonary arterial hypertension.

Background: Endothelin receptor antagonists improve pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2) predispose to PAH. Here, we sought to determine whether there might exist interactions between these 2 signaling pathways and their effect on the acquisition of the altered phenotype of pulmonary artery smooth muscle cells (PA-SMCs) observed in PAH.

Effects of selective endothelin (ET)-A receptor antagonist versus dual ET-A/B receptor antagonist on hearts of streptozotocin-treated diabetic rats.

Aims: The aim was to study the differences in the effectiveness of two types of endothelin (ET) receptor antagonists (selective ET-A or dual ET-A/B antagonists) on the hearts of streptozotocin (STZ)-induced diabetic rats (type I diabetes) at functional and biochemical/molecular levels.

Main Methods: Citrate saline (vehicle) or STZ was injected into rats. The ET-A/B dual receptor antagonist (SB209670, 1mg/kg/day) and the ET-A receptor antagonist (TA-0201, 1mg/kg/day) were then administered to these rats.

Involvement of peptidyl-prolyl isomerase Pin1 in the inhibitory effect of fluvastatin on endothelin-1-induced cardiomyocyte hypertrophy.

Aims: Cardiac hypertrophy is elicited by endothelin (ET)-1 as well as other neurohumoral factors, hemodynamic overload, and oxidative stress; HMG-CoA reductase inhibitors (statins) were shown to inhibit cardiac hypertrophy partly via the anti-oxidative stress. One of their common intracellular pathways is the phosphorylation cascade of MEK signaling. Pin1 specifically isomerizes the phosphorylated protein with Ser/Thr-Pro bonds and regulates their activity through conformational changes.

Downregulated bone morphogenetic protein signaling in nitrofen-induced congenital diaphragmatic hernia.

Purpose: Bone morphogenetic proteins (BMP) have been shown to play crucial roles in not only lung and heart development, but also in the pathogenesis of pulmonary vascular remodeling in pulmonary hypertension (PH). We therefore hypothesized that BMP signaling could be altered in nitrofen-induced congenital diaphragmatic hernia (CDH) and associated PH.

Methods: Pregnant rats were exposed to either 100 mg nitrofen or vehicle on embryonic day (E) 9.

Elevation of plasma basic fibroblast growth factor after nocturnal hypoxic events in patients with obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is associated with recurrent nocturnal hypoxia during sleep; this hypoxia has been implicated in the pathogenesis of cardiovascular complication. However, a useful soluble factor that is sensitively correlated with OSAS severity for the diagnosis remains unidentified. We hypothesized that systemic levels of basic fibroblast growth factor (bFGF), a hypoxia-induced cytokine, were affected by nocturnal hypoxemia in OSAS patients, and we assessed whether the degree of change in the plasma bFGF concentrations before and after nocturnal hypoxia is correlated with the severity of OSAS.

Endothelin-1-induced cardiomyocyte hypertrophy is partly regulated by transcription factor II-F interacting C-terminal domain phosphatase of RNA polymerase II.

Aims: Cardiac hypertrophy is associated with the increase of total amount of RNA, which is in accordance with RNA polymerase II (RNAPII) activation via C-terminal domain (CTD) phosphorylation of the largest subunit of RNAPII. It has been demonstrated that endothelin-1 (ET-1) phosphorylates CTD at the hypertrophic response in cardiomyocytes. However, it is unclear whether ET-1-induced hypertrophy is affected by the CTD phosphatase, transcription factor IIF-interacting CTD phosphatase1 (FCP1).

Prediction of chronic renal insufficiency after coronary angiography by an early increase in oxidative stress and decrease in glomerular filtration rate.

Background: Oxidative stress caused by contrast medium is thought to be one of the main mechanisms of contrast-induced acute kidney injury. A prospective study was conducted to evaluate the relationship between oxidative stress caused by contrast agent administration and long-term renal function.

Methods And Results: Thirty-six consecutive patients who underwent coronary angiography were enrolled.

VEGF promotes tumorigenesis and angiogenesis of human glioblastoma stem cells.

There is increasing evidence for the presence of cancer stem cells (CSCs) in malignant brain tumors, and these CSCs may play a pivotal role in tumor initiation, growth, and recurrence. Vascular endothelial growth factor (VEGF) promotes the proliferation of vascular endothelial cells (VECs) and the neurogenesis of neural stem cells. Using CSCs derived from human glioblastomas and a retrovirus expressing VEGF, we examined the effects of VEGF on the properties of CSCs in vitro and in vivo.

Granulocyte colony-stimulating factor prevents progression of monocrotaline-induced pulmonary arterial hypertension in rats.

Background: Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH.

Methods And Results: Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats.

Continuous intravenous administration of a low dose of epoprostenol greatly decreased serum concentrations of endothelin-1 in primary pulmonary hypertension--a case report.

Endothelin-1 (ET-1) is known to be a principal factor in the pathogenesis of primary pulmonary hypertension (PPH). Recently intravenous administration of epoprosterol improved the survival rate in PPH. However, the effect of epoprosterol on ET-1 remains to be investigated.