Deletion of the gene increases severity of acute lung injury in obese mice.

Previous studies have shown that atrial natriuretic peptide (ANP) attenuates agonist-induced pulmonary edema and that this effect may be mediated in part by the ANP clearance receptor, natriuretic peptide receptor-C (NPR-C). Obesity has been associated with lower plasma ANP levels due to increased expression of NPR-C, and with decreased severity of acute lung injury (ALI). Therefore, we hypothesized that increased expression of NPR-C may attenuate ALI severity in obese populations.

Impact of blood factors on endothelial cell metabolism and function in two diverse heart failure models.

Role of blood-based factors in development and progression of heart failure (HF) is poorly characterized. Blood contains factors released during pathophysiological states that may impact cellular function and provide mechanistic insights to HF management. We tested effects of blood from two distinct HF models on cardiac metabolism and identified possible cellular targets of the effects.

Commercial human pulmonary artery endothelial cells have in-vitro behavior that varies by sex.

It is unknown whether biological sex influences phenotypes of commercially available human pulmonary artery endothelial cells (HPAECs). Ten lots of commercial HPAECs were used (Lonza Biologics; PromoCell). Five (50%) were confirmed to be genotypically male (+) and five (50%) were confirmed to be female (-).

Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension.

Chitinase 3 like 1 (CHI3L1) is the prototypic chitinase-like protein mediating inflammation, cell proliferation, and tissue remodeling. Limited data suggest CHI3L1 is elevated in human pulmonary arterial hypertension (PAH) and is associated with disease severity. Despite its importance as a regulator of injury/repair responses, the relationship between CHI3L1 and pulmonary vascular remodeling is not well understood.

Natriuretic peptide receptor-C mediates the inhibitory effect of atrial natriuretic peptide on neutrophil recruitment to the lung during acute lung injury.

Atrial natriuretic peptide (ANP) protects against acute lung injury (ALI), but the receptor that mediates this effect is not known. Transgenic mice with 0 (knockout), 1 (heterozygote), or 2 (wild-type) functional copies of , the gene that encodes for natriuretic peptide receptor-C (NPR-C), were treated with intravenous infusion of ANP or saline vehicle before oropharyngeal aspiration of (PA103) or saline vehicle. Lung injury was assessed 4 h following aspiration by measurement of lung wet/dry (W/D) weight, whole lung leukocyte and cytokine levels, and protein, leukocyte, and cytokine concentration in bronchoalveolar lavage fluid (BALF).

Agonists for Bitter Taste Receptors T2R10 and T2R38 Attenuate LPS-Induced Permeability of the Pulmonary Endothelium .

One of the hallmarks of acute respiratory distress syndrome (ARDS) is an excessive increase in pulmonary vascular permeability. In settings of ARDS, the loss of barrier integrity is mediated by cell-cell contact disassembly and actin remodelling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability seen in ARDS.

Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts.

Left ventricular remodeling due to pressure overload is associated with poor prognosis. Sacubitril/valsartan is the first-in-class Angiotensin Receptor Neprilysin Inhibitor and has been demonstrated to have superior beneficial effects in the settings of heart failure. The aim of this study was to determine whether sacubitril/valsartan has cardioprotective effect in the early intervention of pressure overloaded hearts and whether it is superior to valsartan alone.

Extracellular vesicles released from p18 overexpressing pulmonary endothelial cells are barrier protective - potential implications for acute respiratory distress syndrome.

The novel endosome protein, p18, and the early endosome GTPase, Rab4, play a significant role in protecting the pulmonary vasculature against permeability associated with acute respiratory distress syndrome. Recently, endothelial-derived extracellular vesicles have been identified to play a key role in the endothelial permeability associated with acute respiratory distress syndrome. Therefore, we investigated the effect of these microparticles, released from endothelial cells overexpressing p18 and Rab4, on pulmonary endothelial barrier function.

Endothelial to mesenchymal transition during neonatal hyperoxia-induced pulmonary hypertension.

Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from mechanical ventilation and hyperoxia, amongst other factors. Although most BPD survivors can be weaned from supplemental oxygen, many show evidence of cardiovascular sequelae in adulthood, including pulmonary hypertension and pulmonary vascular remodeling. Endothelial-mesenchymal transition (EndoMT) plays an important role in mediating vascular remodeling in idiopathic pulmonary arterial hypertension.

Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease.

Endothelial dysfunction is a hallmark of pulmonary arterial hypertension (PAH) but there are no established methods to study pulmonary artery endothelial cells (PAECs) from living patients. We sought to culture PAECs from pulmonary artery catheter (PAC) balloons used during right-heart catheterisation (RHC) to characterise successful culture attempts and to describe PAEC behaviour.PAECs were grown in primary culture to confluence and endothelial cell phenotype was confirmed.

Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.

A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin remodeling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS.

Select Rab GTPases Regulate the Pulmonary Endothelium via Endosomal Trafficking of Vascular Endothelial-Cadherin.

Pulmonary edema occurs in settings of acute lung injury, in diseases, such as pneumonia, and in acute respiratory distress syndrome. The lung interendothelial junctions are maintained in part by vascular endothelial (VE)-cadherin, an adherens junction protein, and its surface expression is regulated by endocytic trafficking. The Rab family of small GTPases are regulators of endocytic trafficking.

Neovascularization in the pulmonary endothelium is regulated by the endosome: Rab4-mediated trafficking and p18-dependent signaling.

Neovascularization, the formation of new blood vessels, requires multiple processes including vascular leak, migration, and adhesion. Endosomal proteins, such as Rabs, regulate trafficking of key signaling proteins involved in neovascularization. The novel endosome protein, p18, enhances vascular endothelial (VE)-cadherin recycling from early endosome to cell junction to improve pulmonary endothelial barrier function.

p18, a novel adaptor protein, regulates pulmonary endothelial barrier function via enhanced endocytic recycling of VE-cadherin.

Vascular permeability is a hallmark of several disease states including acute lung injury (ALI). Endocytosis of VE-cadherin, away from the interendothelial junction (IEJ), causes acute endothelial barrier permeability. A novel protein, p18, anchors to the endosome membrane and plays a role in late endosomal signaling via MAPK and mammalian target of rapamycin.

SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized.

Angiomyolipoma with minimal fat: can it be differentiated from clear cell renal cell carcinoma by using standard MR techniques?

Purpose: To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses.

Materials And Methods: Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated.

Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury.

The pathogenesis of acute lung injury and acute respiratory distress syndrome is characterized by sequestration of leukocytes in lung tissue, disruption of capillary integrity, and pulmonary edema. PKCδ plays a critical role in RhoA-mediated endothelial barrier function and inflammatory responses. We used mice with genetic deletion of PKCδ (PKCδ(-/-)) to assess the role of PKCδ in susceptibility to LPS-induced lung injury and pulmonary edema.

Protection against LPS-induced pulmonary edema through the attenuation of protein tyrosine phosphatase-1B oxidation.

One hallmark of acute lung injury is the disruption of the pulmonary endothelial barrier. Such disruption correlates with increased endothelial permeability, partly through the disruption of cell-cell contacts. Protein tyrosine phosphatases (PTPs) are known to affect the stability of both cell-extracellular matrix adhesions and intercellular adherens junctions (AJs).