Chandran Nagaraj

Chandran Nagaraj
Ludwig Boltzmann Institute for Lung Vascular Research

PhD

About

72
Publications
6,775
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830
Citations
Additional affiliations
January 2012 - present
Medizinische Universität Graz

Publications

Publications (72)
Article
Full-text available
The potassium channel TASK-1, together with other potassium channels controls the low resting tone of pulmonary arteries. The Src family tyrosine kinase (SrcTK) may control potassium channel function in human pulmonary artery smooth muscle cells (hPASMCs) in response to changes in oxygen tension and the clinical use of an SrcTK inhibitor has result...
Article
Full-text available
Cardioprotective benefits of ω-3 fatty acids such as docosahexaenoic acid (DHA) are well established, but the regulatory effect of DHA on vascular tone and pressure in pulmonary hypertension is largely unknown. As DHA is a potent regulator of K ⁺ channels, we hypothesised that DHA modulates the membrane potential of pulmonary artery smooth muscle c...
Article
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 tr...
Article
Full-text available
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 systemati...
Article
Full-text available
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 biocom...
Article
Full-text available
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 tr...
Article
Full-text available
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) channe...
Article
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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. Thus, our study ai...
Article
Introduction A reduction in pulmonary artery (PA) relaxation is a key event in pulmonary arterial hypertension (PAH) pathogenesis. CFTR dysfunction in airway epithelial cells plays a central role in cystic fibrosis (CF); CFTR is also expressed in PAs and has been shown to control endothelium-independent relaxation. Aim and objectives We aimed to d...
Article
Full-text available
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-dioxide (SiO2) 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...
Article
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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 p...
Article
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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 D2 (PGD2) is a potent inflammatory lipid mediator with v...
Article
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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 Ca2+-activated Cl− channels (CaCC). The most prominent member of the CaCC TMEM16A has been sho...
Conference Paper
Background Pulmonary hypertension (PH) is common in patients with fibrosing interstitial lung diseases (ILDs) such as systemic sclerosis (scleroderma) and has a significant impact on survival. The pan-peroxisome proliferator-activated receptor (PPAR) agonist lanifibranor is currently being tested in a phase II clinical trial in scleroderma patients...
Article
Full-text available
This work describes the interaction of the human blood plasma proteins albumin, fibrinogen and γ-globulins with micro-and nano-patterned polymer interfaces. Protein adsorption studies were correlated to the fibrin clotting time of human blood plasma and to the growth of primary human endothelial cells (hECs) on these patterns. It was observed that...
Article
Full-text available
Rationale Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl ⁻ channel TMEM16A gene. Objective We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing PAH. Methods and results We investigat...
Article
Full-text available
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+, Ca2+, Na+ and Cl−). This review focuses on ion channe...
Article
Full-text available
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 exam...
Article
Full-text available
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-...
Article
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The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hyper-tension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to in-vestigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine and kynurenic-acid levels were measured in 20 idiopathic PAH (IPAH) pat...
Article
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Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease in which the amount of emphysema and airway disease may be very different between individuals, even in end-stage disease. Emphysema formation may be linked to the involvement of the small pulmonary vessels. The NAPDH oxidase (Nox) family is emerging as a key disease-related fac...
Article
Aim: Chronic airway diseases such as asthma are associated with increased production of reactive oxygen species (ROS) and oxidative stress. Endogenous NADPH oxidases are a major source of superoxide in lung, but their underlying role in asthma pathology is poorly understood. We sought to characterize the involvement of NADPH oxidase in allergic as...
Article
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Aims: The ATP-binding cassette (ABC)G2 transporter protects the heart from pressure overload-induced ventricular dysfunction but also protects cancer cells from chemotherapeutic agents. It is upregulated in the myocardium of heart failure patients and clears hypoxia-induced intracellular metabolites. This study employs ABCG2 knockout (KO) mice to e...
Article
Polymer based biomaterials particularly polycaprolactone (PCL) are one of the most promising substrates for tissue engineering. The surface chemistry of these materials plays a major role since it governs protein adsorption, cell adhesion, viability, degradation and biocompatibility in the first place. This study correlates the interaction of the m...
Article
Full-text available
Lung cancer is the leading cause of cancer deaths worldwide; survival times are poor despite therapy. The role of the two-pore domain K+ (K2P) channel TASK-1 (KCNK3) in lung cancer is at present unknown. We found that TASK-1 is expressed in non-small cell lung cancer (NSCLC) cell lines at variable levels. In a highly TASK-1 expressing NSCLC cell li...
Data
FACS analysis of caspase 3 activity in H358 cells. H358 cells were incubated under the respective conditions for 72 hours and cells with caspase 3 activity were detected by FACS analysis. Left: representative histogram, M1 indicates apoptotic cells. Right: gating conditions. (PDF)
Data
FACS analysis of caspase 3 activity and EdU incorporation in A549 cells. (A) A549 cells were incubated under the respective conditions for 72 hours and cells with caspase 3 activity were detected by FACS analysis. Left: representative histogram, M1 indicates apoptotic cells. Right: gating conditions. (B) EdU assay in A549 cells. Left: representativ...
Article
Amitriptyline, carbamazepine and gabapentin are often used for the treatment of neuropathic pain. However, their analgesic action on central sensory neurons is still not fully understood. Moreover, the expression pattern of their target ion channels is poorly elucidated in the dorsal horn of the spinal cord. Thus, we performed patch-clamp investiga...
Article
Full-text available
Tumor cells use broad spectrum proteolytic activity of plasmin to invade tissue and form metastatic foci. Cell surface associated enolase-1 (ENO-1) enhances plasmin formation and thus participates in the regulation of pericellular proteolysis. Although increased levels of cell surface bound ENO-1 have been described in different types of cancer, th...
Article
Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate...
Article
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Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized...
Data
Steps involved in the preparation of mouse intrapulmonary arteries. Notes: (A) Heart and lungs were removed en bloc. (B) Removal of the adipose tissue surrounding aorta (arrow). (C) Cutting the aorta exposed the pulmonary artery (arrow). (D) Removal of lung parenchyma exposed further bifurcations (arrow). (E) Further removal of the lung parenchyma...
Data
Representative real-time curve, from isometric tension measurements using a wire myograph. Notes: (A) Duration of vasoconstriction following 0.03 μM U-46619-induced vasoconstriction. (B) Vasorelaxation induced by addition of free iloprost (5 μM) and the nitric oxide donor, sodium nitroprusside (10 μM), on U-46619-induced preconstricted mouse pulmon...
Data
Effects of storage on iloprost encapsulation. Liposomes were stored for 2 months at 4°C and encapsulation was then analyzed by thin layer chromatography. (A) LI-1 and (B) LI-2. Notes: Band for 2 μg iloprost applied as reference (R), bands for liposomal encapsulated iloprost (L), fractions of the obtained flow through (filtrates) containing no ilopr...
Data
Relaxation kinetics of liposomes (empty) and encapsulated iloprost (5 μM iloprost) on isolated mouse pulmonary arteries, following U-46619 preconstriction. (A) LI-1, (B) LI-2, (C) LI-3, (D) LI-4, (E) LI-5, and (F) LI-6. Notes: Relaxation values obtained by empty liposomes were subtracted from the respective liposomal iloprost formulation to determi...
Article
Full-text available
To the Editor: Ma et al. (July 25 issue)(1) report a number of KCNK3 channel gene mutations in patients with pulmonary arterial hypertension that are a novel cause of hereditary pulmonary arterial hypertension. Their observations suggest that the potassium channel TASK-1 plays an important role as controller of the membrane potential and consequent...
Article
Full-text available
Circulating RNA may result from excessive cell damage or acute viral infection and can interact with vascular endothelial cells. Despite the obvious clinical implications associated with the presence of circulating RNA, its pathological effects on endothelial cells and the governing molecular mechanisms are still not fully elucidated. We analyzed t...
Data
Morphological characterization of endothelial cells from surgical PEA material. (A) Mixed culture of cells growing out from the PEA material. Significant proportion of cells show vWF positive signal (brown). (B) Purified, vWF (brown) positive endothelial culture after CD31 magnetic bead sorting. (C) Lack of the staining for smooth muscle α-actin in...
Data
Bar graphs represent percentage of apoptotic cells as measured by PI and Annexin V staining upon 24 hours of stimulation (Stauro - staurosporin; ***p<0.001 as compared to Control). (TIF)
Data
Quantitative RT-PCR of TLR3 and apoptosis measurements in hPAECs. (DOCX)
Article
Introduction: The molecular pathways leading to right ventricular dysfunction in pulmonary hypertension (PH) are poorly understood. ABCG2 is a cell membrane transporter with effective drug transport ability protecting against intracellularly accumulated toxic metabolites. It provides cell survival advantage under hypoxic conditions and oxidative st...
Article
Full-text available
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease with persistent thrombotic occlusion or stenosis of the large pulmonary arteries resulting in pulmonary hypertension. Surgical removal of the neointimal layer of these vessels together with the non-resolved thrombus consisting of organized collagen-rich fibrotic areas with part...
Data
Migration and vessel formation ability of CTEPH-hECs and hPAECs. (A) Representative image (4X) of vessel formation on Matrigel® after 21h of CTEPH-hECs and hPAECs. (B) Bar graph shows summarized results of vessel formation assay as number of loops formed (number of experiments n = 3). (C) Representative images of migration assay of CTEPH-hECs and h...
Article
Full-text available
As powerful vasodilators, prostacyclin analogues are presently the mainstay in the treatment of severe pulmonary arterial hypertension. Although the hemodynamic effects of prostacyclin analogues are well known, the molecular mechanism of their acute effects on pulmonary vascular tone and systemic vascular tone remains poorly understood. Peroxisome...