- Pulmonary Hypertension Research and Treatments
- Nitric Oxide and Endothelin Effects
- Ion Channels and Receptors
- Ion channel regulation and function
- Angiogenesis and VEGF in Cancer
- Neonatal Respiratory Health Research
- Alzheimer's disease research and treatments
- Phosphodiesterase function and regulation
- Cancer, Hypoxia, and Metabolism
- Ion Transport and Channel Regulation
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Congenital heart defects research
- Respiratory Support and Mechanisms
- Receptor Mechanisms and Signaling
- Barrier Structure and Function Studies
- Renin-Angiotensin System Studies
- Caveolin-1 and cellular processes
- Enzyme function and inhibition
- Cardiovascular Function and Risk Factors
- Vibrio bacteria research studies
- Bacterial biofilms and quorum sensing
- Cardiac electrophysiology and arrhythmias
- ATP Synthase and ATPases Research
- Neuroinflammation and Neurodegeneration Mechanisms
University of South Alabama
2015-2024
Lawrence Berkeley National Laboratory
2023
Amsterdam University Medical Centers
2022
Cornell University
2020
National Institutes of Health
2020
Yale University
2020
Harvard University
2020
Rockefeller University
2020
Brigham and Women's Hospital
2020
Princeton University
2020
The plexiform lesions of severe pulmonary arterial hypertension (PAH) are similar in histologic appearance, whether the disease is idiopathic or secondary. Both forms show actively proliferating endothelial cells without evidence apoptosis. Here, we discuss pathobiology atypical, angioproliferative PAH. concept cell as a "quasi-malignant" provides new framework for antiproliferative, antiangiogenic therapy
Endothelial progenitor cells (EPCs) have been isolated postnatally from bone marrow, blood, and both the intima adventitia of conduit vessels. However, it is unknown whether EPCs can be lung microcirculation. Thus we sought to determine microvasculature possesses capable de novo vasculogenesis. Rat pulmonary artery (PAEC) microvascular (PMVEC) endothelial were selected by using a single-cell clonogenic assay. Whereas majority PAECs (approximately 60%) fully differentiated, PMVECs 75%)...
Pulmonary microvascular endothelial cells possess both highly proliferative and angiogenic capacities, yet it is unclear how these sustain the metabolic requirements essential for such growth. Rapidly proliferating rely on aerobic glycolysis to growth, which characterized by glucose consumption, fermentation lactate, lactic acidosis, all in presence of sufficient oxygen concentrations. Lactate dehydrogenase A converts pyruvate lactate necessary rapid flux through glycolysis. We therefore...
Pseudomonas aeruginosa pneumonia elicits endothelial cell release of cytotoxic amyloids that can be recovered from the bronchoalveolar lavage and cerebrospinal fluids critically ill patients. Introduction these into lateral ventricle impairs learning memory in mice. However, it is unclear whether lung origin (1) are neurotropic, (2) cause structural remodeling hippocampal dendrites. Thus, we used electrophysiological studies brain slices analysis post-mortem tissues obtained animals exposed...
Endothelial cell (EC) apoptosis and proliferation of apoptosis-resistant cells is a hallmark pulmonary hypertension (PH). Yet, why some ECs die others proliferate how this contributes to vascular remodeling unclear. We hypothesized that differential response may: (1) relate different EC subsets, namely artery (PAECs) versus microvascular (MVECs); (2) be attributable autophagic activation in both subtypes; (3) cause replacement MVECs by PAECs with subsequent distal vessel muscularization.
Cytosolic Ca 2+ concentration ([Ca ] i ) plays an important role in control of pulmonary vascular endothelial cell (ECs) barrier function. In this study, we investigated whether thapsigargin- and ionomycin-induced changes cytosolic induce permeability rat microvascular (RPMV) versus macrovascular (RPA) ECs. Transwell cultures, RPMVECs formed a tighter, more restrictive than RPAECs to 12,000-, 72,000-, 150,000-molecular-weight FITC-labeled dextrans. Thapsigargin (1 μM) produced higher [Ca...
The farnesoid X receptor (FXR) is a member of the nuclear superfamily that highly expressed in liver, kidney, adrenals, and intestine. FXR may play an important role pathogenesis cardiovascular diseases via regulating metabolism transport cholesterol. In this study, we report also rat pulmonary artery endothelial cells (EC), "nonclassical" bile acid target tissue. functional EC, as demonstrated by induction its genes such small heterodimer partner (SHP) after treatment with chenodeoxycholic...
Activation of Ca 2+ entry is known to produce endothelial cell shape change, leading increased permeability, leukocyte migration, and initiation angiogenesis in conduit-vessel cells. The mode regulating unknown. We hypothesized that activation store-operated channels (SOCs) sufficient promote change necessary for these processes. SOC rat pulmonary arterial cells free cytosolic was dependent on a membrane current having net inward component 5.45 ± 0.90 pA/pF at −80 mV. Changes accompanied...
Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause sporadic human infections with a high fatality rate. Respiratory failure due acute respiratory distress syndrome (ARDS) is complication among hospitalized patients. Since progressive pulmonary endothelial damage the hallmark of ARDS, we investigated host responses following HPAI virus infection microvascular cells. Evaluation these cells for presence receptors preferred by demonstrated that avian-like (α2-3-linked) were...
Transmembrane heparan sulfate proteoglycans regulate multiple aspects of cell behavior, but the molecular basis their signaling is unresolved. The major family transmembrane syndecans, present in virtually all nucleated cells, with mostly unknown functions. Here, we show that syndecans transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent behavior. In fibroblasts, ligand interactions syndecan-4 recruit cytoplasmic protein kinase C...
Exoenzyme Y (ExoY) is a Pseudomonas aeruginosa toxin that introduced into host cells through the type 3 secretion system (T3SS). Once inside cell cytoplasm, ExoY generates cyclic nucleotides cause tau phosphorylation and microtubule breakdown. Microtubule breakdown causes interendothelial gap formation tissue edema. Although transiently induces formation, it remains unclear whether prevents repair of endothelial barrier. Here, we test hypothesis intoxication impairs recovery barrier...
Activated leukocyte cell adhesion molecule (ALCAM) (CD166) is an immunoglobulin that has been implicated in migration. The present study examined the expression of ALCAM human breast cancer and assessed its prognostic value. immunohistochemical distribution location was normal tissue carcinoma. levels transcripts frozen (normal breast, n = 32; cancer, 120) were determined using real-time quantitative PCR. results then analyzed relation to clinical data including tumor type, grade, nodal...
Mammalian transmembrane adenylyl cyclases synthesize a restricted plasmalemmal cAMP pool that is intensely endothelial barrier protective. Bacteria have devised mechanisms of transferring eukaryotic factor-dependent into mammalian cells. Pseudomonas aeruginosa ExoY one such enzyme catalyzes cytosolic synthesis, with unknown function. genetically modified to introduce only the toxin elevated 800-fold in pulmonary microvascular cells over 4 hours, whereas catalytically deficient (ExoY(K81M))...