Lipid Ratios for Diagnosis and Prognosis of Pulmonary Hypertension.

Pulmonary hypertension (PH) poses a significant health threat. Current biomarkers for PH lack specificity and have poor prognostic capabilities. To develop better biomarkers for PH that are useful for patient identification and management.

Functionalization of Polycaprolactone 3D Scaffolds with Hyaluronic Acid Glycine-Peptide Conjugates and Endothelial Cell Adhesion.

This study enhances the bioactivity of polycaprolactone (PCL) scaffolds for tissue engineering by functionalizing them with oxidized hyaluronic acid glycine-peptide conjugates to improve endothelial cell adhesion and growth. Hyaluronic acid was conjugated with a glycine-peptide to create a bioactive interface on PCL (static water contact angle, SCA(HO): 98°). The scaffolds were fabricated using a melt extrusion 3D printing technique.

Pulmonary vascular remodeling in Fra-2 transgenic mice is driven by type 2 inflammation and accompanied by pulmonary vascular hyperresponsiveness.

Lung vessel remodeling leads to increased pulmonary vascular resistance, causing pulmonary arterial hypertension (PAH), and consequently right ventricular hypertrophy and failure. In patients suffering from systemic sclerosis (SSc), PAH can occur and is a life-threatening complication. Dysregulation of immune processes plays a crucial role in pulmonary vascular remodeling, as has previously been shown in Fos-related antigen-2 (Fra-2) transgenic (TG) mice, a model of SSc-PAH.

Protocol for the fabrication of self-standing (nano)cellulose-based 3D scaffolds for tissue engineering.

Three-dimensional (3D) and porous scaffolds made from nanocellulosic materials hold significant potential in tissue engineering (TE). Here, we present a protocol for fabricating self-standing (nano)cellulose-based 3D scaffolds designed for in vitro testing of cells from skin and cartilage tissues. We describe steps for preparation of nanocellulose ink, scaffold formation using 3D printing, and freeze-drying.

Antithrombogenic polysaccharide coatings to improve hemocompatibility, protein-repellence, and endothelial cell response.

Polyester biomaterials play a crucial in vascular surgery, but suffer from unspecific protein adsorption, thrombogenicity, and inadequate endothelial cell response, which limit their success. To address these issues, we investigated the functionalization of polyester biomaterials with antithrombogenic polysaccharide coatings. A two-step and water-based method was used to coat cationized polycaprolactone with different sulfated polysaccharides (SPS), which resulted in long-term stability, tunable morphology, roughness, film thickness, chemical compositions, zeta potential, and water content.

The TREK-1 potassium channel is a potential pharmacological target for vasorelaxation in pulmonary hypertension.

Background And Purpose: Pulmonary arterial hypertension (PAH) is a progressive disease in which chronic membrane potential (E) depolarisation of the pulmonary arterial smooth muscle cells (PASMCs) causes calcium overload, a key pathological alteration. Under resting conditions, the negative E is mainly set by two pore domain potassium (K) channels, of which the TASK-1 has been extensively investigated.

Experimental Approach: Ion channel currents and membrane potential of primary cultured human(h) PASMCs were measured using the voltage- and current clamp methods.

3D-Printed Collagen-Nanocellulose Hybrid Bioscaffolds with Tailored Properties for Tissue Engineering Applications.

Hybrid collagen (Coll) bioscaffolds have emerged as a promising solution for tissue engineering (TE) and regenerative medicine. These innovative bioscaffolds combine the beneficial properties of Coll, an important structural protein of the extracellular matrix, with various other biomaterials to create platforms for long-term cell growth and tissue formation. The integration or cross-linking of Coll with other biomaterials increases mechanical strength and stability and introduces tailored biochemical and physical factors that mimic the natural tissue microenvironment.

Lipidomics for diagnosis and prognosis of pulmonary hypertension.

Background: Pulmonary hypertension (PH) poses a significant health threat with high morbidity and mortality, necessitating improved diagnostic tools for enhanced management. Current biomarkers for PH lack functionality and comprehensive diagnostic and prognostic capabilities. Therefore, there is a critical need to develop biomarkers that address these gaps in PH diagnostics and prognosis.

Chloride channels in the lung: Challenges and perspectives for viral infections, pulmonary arterial hypertension, and cystic fibrosis.

Fine control over chloride homeostasis in the lung is required to maintain membrane excitability, transepithelial transport as well as intra- and extracellular ion and water homeostasis. Over the last decades, a growing number of chloride channels and transporters have been identified in the cells of the pulmonary vasculature and the respiratory tract. The importance of these proteins is underpinned by the fact that impairment of their physiological function is associated with functional dysregulation, structural remodeling, or hereditary diseases of the lung.

Potassium Channels in the Transition from Fetal to the Neonatal Pulmonary Circulation.

The transition from the fetal to the neonatal circulation includes dilatation of the pulmonary arteries (PA) and closure of the Ductus Arteriosus Botalli (DAB). The resting membrane potential and various potassium channel activities in smooth muscle cells (SMC) from fetal and neonatal PA and DAB obtained from the same species has not been systematically analyzed. The key issue addressed in this paper is how the resting membrane potential and the whole-cell potassium current (IK) change when PASMC or DABSMC are transitioned from hypoxia, reflecting the fetal state, to normoxia, reflecting the post-partal state.

One-Step Fabrication of Hollow Spherical Cellulose Beads: Application in pH-Responsive Therapeutic Delivery.

The path to greater sustainability and the development of polymeric drug delivery systems requires innovative approaches. The adaptation and use of biobased materials for applications such as targeted therapeutic delivery is, therefore, in high demand. A crucial part of this relates to the development of porous and hollow structures that are biocompatible, pH-responsive, deliver active substances, and contribute to pain relief, wound healing, tissue regeneration, and so forth.

Revisiting the Large-Conductance Calcium-Activated Potassium (BKCa) Channels in the Pulmonary Circulation.

Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell's membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits.

RGS5 Determines Neutrophil Migration in the Acute Inflammatory Phase of Bleomycin-Induced Lung Injury.

The regulator of G protein signaling (RGS) represents a widespread system of controllers of cellular responses. The activities of the R4 subfamily of RGSs have been elucidated in allergic pulmonary diseases. However, the R4 signaling in other inflammatory lung diseases, with a strong cellular immune response, remained unexplored.

Involvement of CFTR in the pathogenesis of pulmonary arterial hypertension.

Introduction: A reduction in pulmonary artery relaxation is a key event in the pathogenesis of pulmonary arterial hypertension (PAH). Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in airway epithelial cells plays a central role in cystic fibrosis; CFTR is also expressed in pulmonary arteries and has been shown to control endothelium-independent relaxation.

Aim And Objectives: We aimed to delineate the role of CFTR in PAH pathogenesis through observational and interventional experiments in human tissues and animal models.

Anticoagulant Activity of Cellulose Nanocrystals from Isora Plant Fibers Assembled on Cellulose and SiO Substrates via a Layer-by-Layer Approach.

In this study, we report the isolation of cellulose nanocrystals (CNCs) from Isora plant fibers by sulfuric acid hydrolysis and their assembly on hydrophilic cellulose and silicon-di-oxide (SiO) surfaces via a layer-by-layer (LBL) deposition method. The isolated CNCs were monodispersed and exhibited a length of 200-300 nm and a diameter of 10-20 nm, a negative zetapotential (-34-39 mV) over a wide pH range, and high stability in water at various concentrations. The multi-layered structure, adsorbed mass, conformational changes, and anticoagulant activity of sequentially deposited anionic (sulfated) CNCs and cationic polyethyleneimine (PEI) on the surfaces of cellulose and SiO by LBL deposition were investigated using a quartz crystal microbalance technique.

ERS International Congress, Madrid, 2019: highlights from the Pulmonary Vascular Diseases Assembly.

The 2019 European Respiratory Society (ERS) International Congress, held in Madrid, Spain, had exciting sessions regarding the field of pulmonary vascular disease. The symposia related to the new ERS/European Society of Cardiology (ESC) Guidelines for the diagnosis and management of acute pulmonary embolism were well received, as were sessions on pulmonary hypertension related to lung disease, demonstrating the concept of pulmonary hypertension not being the rarity that it was previously thought to be. The use of risk stratification in relation to pulmonary arterial hypertension (PAH) was heavily featured and the scientific sessions informing the respiratory community of potential biomarkers and targets for future therapies were thought-provoking.

Prostaglandin D strengthens human endothelial barrier by activation of E-type receptor 4.

Life-threatening inflammatory conditions such as acute respiratory distress syndrome or sepsis often go hand in hand with severe vascular leakage. During inflammation, endothelial cell integrity and intact barrier function are crucial to limit leukocyte and plasma extravasation. Prostaglandin D (PGD) is a potent inflammatory lipid mediator with vasoactive properties.

Endothelial Dysfunction Following Enhanced TMEM16A Activity in Human Pulmonary Arteries.

Endothelial dysfunction is one of the hallmarks of different vascular diseases, including pulmonary arterial hypertension (PAH). Ion channelome changes have long been connected to vascular remodeling in PAH, yet only recently has the focus shifted towards Ca-activated Cl channels (CaCC). The most prominent member of the CaCC TMEM16A has been shown to contribute to the pathogenesis of idiopathic PAH (IPAH) in pulmonary arterial smooth muscle cells, however its role in the homeostasis of healthy human pulmonary arterial endothelial cells (PAECs) and in the development of endothelial dysfunction remains underrepresented.

Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension.

Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl channel TMEM16A gene. We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing pulmonary arterial hypertension (PAH).We investigated healthy donor lungs (n=40) and recipient lungs with IPAH (n=38) for the expression of anion channel and transporter genes in small pulmonary arteries and pulmonary artery smooth muscle cells (PASMCs).

Ion Channels in Pulmonary Hypertension: A Therapeutic Interest?

Pulmonary arterial hypertension (PAH) is a multifactorial and severe disease without curative therapies. PAH pathobiology involves altered pulmonary arterial tone, endothelial dysfunction, distal pulmonary vessel remodeling, and inflammation, which could all depend on ion channel activities (K⁺, Ca, Na⁺ and Cl). This review focuses on ion channels in the pulmonary vasculature and discusses their pathophysiological contribution to PAH as well as their therapeutic potential in PAH.

Rho-Kinase Inhibition Ameliorates Dasatinib-Induced Endothelial Dysfunction and Pulmonary Hypertension.

The multi-kinase inhibitor dasatinib is used for treatment of imatinib-resistant chronic myeloid leukemia, but is prone to induce microvascular dysfunction. In lung this can manifest as capillary leakage with pleural effusion, pulmonary edema or even pulmonary arterial hypertension. To understand how dasatinib causes endothelial dysfunction we examined the effects of clinically relevant concentrations of dasatinib on both human pulmonary arterial macro- and microvascular endothelial cells (ECs).

TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications.

TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. This gene subfamily is constitutively active at physiological resting membrane potentials in excitable cells, including smooth muscle cells, and has been particularly linked to the human pulmonary circulation. TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways.