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Endothelial Interleukin-17 Receptor D (Il17rd) Promotes Western Diet-Induced Aortic Myeloid Cell Infiltration, Shivangi Pande

Electronic Theses and Dissertations

The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor), belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent monocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83% compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 cells …

The Angiogenic Potential Of Ph-Neutral Borophosphate Bioactive Glasses, Bradley A. Bromet, Nathaniel P. Blackwell, Nada Abokefa, Parker Freudenberger, Rebekah L. Blatt, Richard K. Brow, Julie A. Semon

Materials Science and Engineering Faculty Research & Creative Works

Borate bioactive glasses have gained attention in recent years due to their therapeutic and regenerative effects in vivo. However, borate bioactive glasses release alkaline ions, increasing the local pH and creating a toxic environment for cell culture studies. A partial compositional substitution of phosphate for borate can create a pH-neutral glass that does not significantly affect the local pH while still releasing therapeutic ions. In the present study, a series of Na-Ca-borophosphate bioactive glasses with different borate-to-phosphate ratios was evaluated in vitro and in vivo for cytotoxicity and angiogenic effects. Compared to more basic borate glasses, the pH-neutral glasses supported …

Producing And Measuring Oscillatory Shear In A Novel Microfluidic Chip, Sanaz Lordfard, Daniel Lorusso, Tamie L. Poepping, Hristo N Nikolov, Kayla Soon, Stephen Sims, Jeffrey Dixon, David Holdsworth

Undergraduate Student Research Internships Conference

Purpose: To demonstrate the effectiveness of a novel microfluidic device mimicking oscillatory blood flow, allowing cell biologists to examine how endothelial cells respond to a range of oscillatory shear stress levels.

Methods: The microfluidic chip consists of a circular-shaped reservoir, leading to a rectangular channel that is examined under a microscope. The plunger is connected to a speaker system and oscilloscope, allowing the plunger to apply a range of frequencies (5-60Hz) and voltages (5-10 V, leading to a variety in oscillation amplitudes) to the reservoir region. 1.1 um fluorescent particles diluted in distilled water were used for tracking. Processing was …

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …

Endothelial Cell-Specific Deletion Of A Microrna Accelerates Atherosclerosis, Dafeng Yang, Stefan Haemmig, Jingshu Chen, Michael Mccoy, Henry S. Cheng, Haoyang Zhou, Daniel Pérez-Cremades, Xiao Cheng, Xinghui Sun, Jorge Haneo-Mejia, Shamsudheen K. Vellarikkal, Rajat M. Gupta, Victor Barrera, Mark W. Feinberg

Department of Biochemistry: Faculty Publications

Background and aims: Chronic vascular endothelial inflammation predisposes to atherosclerosis; however, the cell-autonomous roles for endothelial-expressing microRNAs (miRNAs) are poorly understood in this process. MiR-181b is expressed in several cellular constituents relevant to lesion formation. The aim of this study is to examine the role of genetic deficiency of the miR-181b locus in endothelial cells during atherogenesis.

Methods and Results: Using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-induced atherosclerosis mouse model, we demonstrated that endothelial cell (EC)-specific deletion of miR-181a2b2 significantly promoted atherosclerotic lesion formation, cell adhesion molecule expression, and the influx of lesional macrophages in the vessel wall. Yet, …

The Role Of Ehd2 In Endothelial Cells, Rachael Judson

Electronic Theses and Dissertations

The role of EHD2 in terms of Cav1 interaction had not been previously characterized and was the main goal of this research. Cav1 has been shown to lead to the ubiquitination of Rac1. Because of this, the role of EHD2 in Rac1 regulation was investigated. An increase in long-term migration in endothelial cells was observed and suggested that EHD2 impacts the RhoA pathway instead of the Rac1 pathway. This lead to the hypothesis that EHD2 controls a part of the RhoA pathway. This hypothesis is supported by the loss of filamentous actin and an increase in serrated junctions in cells …

Expression Of Sars Cov2 Receptors Influenced Upon Cytokine Polarizations (Il-4 And Ifnγ) In Hemangioendothelioma Cells, Chandra Lekha Koopari

Browse all Theses and Dissertations

Endothelial cells are distinct multifunctional cells with essential metabolic and synthetic roles along with their ability to function as selective permeability barrier. Endothelial cells (ECs), the major component of blood vessels, essentially interact directly yet differently with inflammatory cytokines. ECs are well recognized to be polarized cells, but little is known about the potential function of inflammatory mediators. Covid 19 may have long-term health effects on par with chronic illnesses. Vascular inflammatory disease and coagulopathy linked to COVID-19 are exacerbated by endothelial cell (EC) dysfunction. SARS-CoV-2 enters the host cell through the Angiotensin Converting Enzyme 2 (ACE2) receptor and primes …

Mrna-Sequencing Pipeline For Differential Gene Expression Analysis, Crystal Han

Master's Projects

Endothelial cells (ECs) line the insides of blood vessels and play a key role in the coagulation and vascular repair system. Under normal circumstances, ECs are constantly expressing anticoagulants to prevent clots and maintain healthy blood flow. But when there is an injury to the vessel, endothelial cells become centrally involved in orchestrating the complex series of events that would lead to the clotting of the wound. Thus, ECs are dynamic and respond accordingly based on changes in their local environment. Unfortunately, endothelial cells can sometimes misinterpret cues from the environment and initiate coagulation when there is no vessel damage …

The Role Of Neuropilin-1 In Covid-19, Bindu Mayi, Jillian A. Leibowitz, Arden T. Woods, Katherine A. Ammon, Alphonse E. Liu, Aarti Raja

Biology Faculty Articles

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Fluid Shear Stress And Endothelial Cells Synergistically Promote Osteogenesis Of Mesenchymal Stem Cells Via Integrin Ss1-Fak-Erk1/2 Pathway, Mingli Jiang, Qihua Shen, Yi Zhou, Wenxia Ren, Miaomiao Chai, Yan Zhou, Wen-Song Tan

Turkish Journal of Biology

Prevascularization and mechanical stimulation have been reported as effective methods for the construction of functional bone tissue. However, their combined effects on osteogenic differentiation and its mechanism remain to be explored. Here, the effects of fluid shear stress (FSS) on osteogenic differentiation of rat bone-marrow-derived mesenchymal stem cells (BMSCs) when cocultured with human umbilical vein endothelial cells (HUVECs) were investigated, and underlying signaling mechanisms were further explored. FSS stimulation for 1-4 h/day increased alkaline phosphatase (ALP) activity and calcium deposition in coculture systems and promoted the proliferation of cocultured cells. FSS stimulation for 2 h/day was selected as the optimized …

Focal Adhesion Kinase And Src Mediate Microvascular Hyperpermeability Caused By Fibrinogen- Γc- Terminal Fragments, Richard S. Beard Jr.

Biomolecular Research Institute Publications and Presentations

Objectives

We previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvβ3, a transmembrane integrin receptor involved in intracellular signaling mediated by the tyrosine kinases FAK and Src, we hypothesized that γC alters endothelial barrier function by activating the FAK-Src pathway leading to junction dissociation and RhoA driven cytoskeletal stress-fiber formation.

Methods and results

Using intravital microscopy of rat mesenteric microvessels, we show increased extravasation …

Upregulation Of Psmd4 Gene By Hypoxia In Prostate Cancer Cells, Sümeyye Aydogan Türkoğlu, Gi̇zem Dayi, Feray Köçkar

Turkish Journal of Biology

Ubiquitin-proteasome pathways have a crucial role in tumor progression. PSMD4 (Rpn10, 26S proteasome non-ATPase subunit 4), which is a subunit of the regulatory particle, is a major ubiquitin (Ub) receptor of 26S proteasome. PSMD4 overexpression has been observed in colon carcinoma, hepatocellular carcinoma, and breast cancer. In this work, we elucidated the effect of hypoxia on PSMD4 gene expression in prostate cancer cells (PC3). Chemically mimicked hypoxia drastically upregulated PSMD4 gene expression at both mRNA and protein levels. Transient transfection experiments indicated that all promoter fragments were active in PC3 cells. Hypoxia increased transcriptional activity of all PSMD4 promoter constructs. …

Endoglin Protein Interactome Profiling Identifies Trim21 And Galectin-3 As New Binding Partners, Eunate Gallardo-Vara, Lidia Ruiz-Llorente, Juan Casado-Vela, María J. Ruiz-Rodríguez, Natalia López-Andrés, Asit K. Pattnaik, Miguel Quintanilla

School of Veterinary and Biomedical Sciences: Faculty Publications

Endoglin is a 180-kDa glycoprotein receptor primarily expressed by the vascular endothelium and involved in cardiovascular disease and cancer. Heterozygous mutations in the endoglin gene (ENG) cause herediatry hemorrhagic telangiectasia type 1, a vascular disease that presents with nasal and gastrointestinal bleeding, skin and mucosa telangiectase, and arteriovenous malformations in internal organs. A circulating form of endoglin (alias soluble endoglin, sEng), proteolytically released from the membrane-bound protein, has been observed in several inflammation-related pathological conditions and appears to contribute to endothelial dysfunction and cancer development through unknown mechanisms. Membrane-bound endoglin is an auxiliary component of the TGF-B receptor complex and …

Neutrophil Extracellular Traps And Vascular Barrier Injury, Jamie E. Meegan

USF Tampa Graduate Theses and Dissertations

Sepsis is a life-threatening inflammatory condition with high morbidity and mortality rates. Though improvements to diagnosis and management of sepsis have been made, the complexity of the disease process and an incomplete understanding of its endpoint mechanisms have prevented major breakthroughs for early diagnosis and treatment. Representing a common endpoint in a number of inflammatory injuries including sepsis, endothelial barrier dysfunction causes fluid leakage and leukocyte infiltration that leads to tissue damage and multiple organ failure. Therefore, elucidating mechanisms of endothelial barrier regulation is needed to further develop targeted therapies in inflammatory disease.

Sepsis is characterized by a hyperinflammatory response …

A Comparison Of Resveratrol And Other Polyphenolic Compounds On Notch Activation And Endothelial Cell Activity, Bryce Lafoya, Jordan A. Munroe, Allan R. Albig

Biology Faculty Publications and Presentations

Resveratrol is a polyphenolic compound produced by plants which makes its way into the human diet through plant-based foods. It has been shown to provide many health benefits, helping to ward of age-related diseases and promoting cardiovascular health. Additionally, resveratrol is a potent activator of the Notch signaling pathway. While resveratrol receives the most attention as a polyphenolic nutraceutical, other compounds with similar structures may be more potent regulators of specific cellular processes. Here, we compare resveratrol, apigenin, chrysin, genistein, luteolin, myricetin, piceatannol, pterostilbene, and quercetin for their ability to regulate Notch signaling. In addition, we compare the ability of …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

Exosomes Released From Multiple Myeloma Cells Influence The Angiogenic Function Of Endothelial Cells By Regulating Microrna-29b, Qinmao Ye

Browse all Theses and Dissertations

Multiple myeloma is a hematological malignancy characterized by clonal proliferation of plasma cells generally caused by chromosomal abnormalities. It occurs in the bone marrow, which is the microenvironment of multiple myeloma. Exosomes (EXs) are 30-100 nm membrane-derived micro-vesicles containing various of bioactive molecules, such as microRNAs, to mediate the cell-cell interaction. Numerous studies reported that exosomes play a significant role in tumor microenvironment. Angiogenesis has the important implication in tumor exacerbation to supply nutrients to promote the progression of cancer cells through endothelial cells (ECs). Some studies demonstrated that microRNA-29b (miR-29b) can suppress tumor development and inhibit angiogenesis. Therefore, in …

Phenotypically Heterogeneous Podoplanin-Expressing Cell Populations Are Associated With The Lymphatic Vessel Growth And Fibrogenic Responses In The Acutely And Chronically Infarcted Myocardium, M Cimini, A Cannata, G Pasquinelli, Marcello Rota, P Goichberg

NYMC Faculty Publications

Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

A Biochemical Approach To Define The Interactome For Calpain2 In Endothelial Cells, Dorothy E. Croall Phd, Jordan R. Hoffman Ms, Calvin Ph Vary Phd, Sharon L. Ashworth Phd, Billy R. Chase, Jay Beaudoin Ii

Molecular & Biomedical Sciences Faculty Scholarship

Current repositories for protein-protein interactions and high throughput screening methods focus on individual gene products and do not consider the significance of calcium induced conformational changes. These limitations suggest the need for alternative strategies to better define the calpain2 interactome. Affinity capture coupled with LC-MS/MS and proteomic analysis of the recovered proteins provides a powerful approach to identify protein-protein interactions for the heterodimeric calpain2. CAPN2 (rat) was modified to be catalytically incompetent (C105A) and fused with a C-terminal 15 residue peptide optimized for biotinylation by the biotin protein ligase, BirA. The resulting CAPN2*, heterodimerized with truncated CAPNS1, was purified from …

Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large

Physiology and Pharmacology Publications

The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …

Decorin As A Multivalent Therapeutic Agent Against Cancer., Thomas Neill, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin is a prototypical small leucine-rich proteoglycan that epitomizes the multifunctional nature of this critical gene family. Soluble decorin engages multiple receptor tyrosine kinases within the target-rich environment of the tumor stroma and tumor parenchyma. Upon receptor binding, decorin initiates signaling pathways within endothelial cells downstream of VEGFR2 that ultimately culminate in a Peg3/Beclin 1/LC3-dependent autophagic program. Concomitant with autophagic induction, decorin blunts capillary morphogenesis and endothelial cell migration, thereby significantly compromising tumor angiogenesis. In parallel within the tumor proper, decorin binds multiple RTKs with high affinity, including Met, for a multitude of oncosuppressive functions including growth inhibition, tumor cell …

Investigation Into The Function Of Endothelial Cells And Their Signaling In Early Salivary Gland Development, Hae Ryong Kwon

Legacy Theses & Dissertations (2009 - 2024)

Functional vasculature regulates organ formation and regeneration. Perfusion-independent and nutrition-independent endothelial regulation of epithelial patterning is of considerable interest for application in restoring parenchymal function. During murine submandibular salivary gland development, the vasculature co-develops with the epithelium; however, it is still unknown if the vasculature has instructive effects on the epithelium. A systems biological study revealed that endothelial genes are enriched in epithelial clefts, suggesting a potential involvement of endothelial cells in early morphogenesis. Using immunodepletion of the endothelial cells from the mesenchyme of reconstituted glands, a requirement for endothelial cells in epithelial patterning was demonstrated. Specifically, lobule formation was …

Novel Mechanism Of Attenuation Of Lps-Induced Nf-Kappab Activation By The Heat Shock Protein 90 Inhibitor, 17-N-Allylamino-17-Demethoxygeldanamycin, In Human Lung Microvascular Endothelial Cells, Gagan S. Thangjam, Christiana Dimitropoulou, Atul D. Joshi, Nektarios Barabutis, Mary C. Shaw, Yevgeniy Kovalenkov, Christopher M. Wallace, David J. Fulton, Vijay Patel, John D. Catravas

Bioelectrics Publications

Heat shock protein (hsp) 90 inhibition attenuates NF-kappaB activation and blocks inflammation. However, the precise mechanism of NF-kappaB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-kappaB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-kappaB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein-protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG-induced …

Resolution Of Central Nervous System Astrocytic And Endothelial Sources Of Ccl2 Gene Expression During Evolving Neuroinflammation, Bandana Shrestha, Shujun Ge, Joel S. Pachter

UCHC Articles - Research

Background

The chemokine CCL2 is a critical mediator of neuroinflammation in diseases such as multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). CCL2 drives mononuclear cell infiltration into the central nervous system (CNS), alters expression and distribution of microvascular endothelial tight junction proteins, and disrupts the blood–brain and blood-spinal cord barriers. Immunohistochemistry has consistently revealed astrocytes to be a source of this chemokine during neuroinflammation, while providing less uniform evidence that CNS endothelial cells may also express CCL2. Moreover, the relative contributions of these cell types to the CNS pool of CCL2 during MS/EAE are unclear and …

Effects Of Prematurity On The Presence Of Weibel-Palade Bodies In Human Umbilical Vein Endothelial Cells In Situ, Niloufar Tabatabeai, Dr. John S. Gardner

Journal of Undergraduate Research

Newbom, premature infants have greater susceptibility to infection compared to older newborn infants. Although the reason for greater susceptibility to bacterial infection in premature infants is unknown, there are many reports that focus on neutrophils as the defective cell type in the immature neonatal system. However, it was recently reported by Lorant et al. that in a rat model of inflammation, neutrophils from adult rats failed to migrate efficiently in neonatal rats.’ Furthermore, we found that this defect was associated with decreased expression of Pselectin on the surface of neonatal endothelial cells in situ.

Neuropilin In The Vascular System: Mechanistic Basis Of Angiogenesis, Hou-Fu Guo

Theses and Dissertations--Molecular and Cellular Biochemistry

The vascular system is critical for maintaining homeostasis in all vertebrates. Structural studies of Neuropilin (Nrp), an essential angiogenic receptor, have defined its role in regulating angiogenesis, the formation of new vessels from the existing vasculature. Utilizing biochemical and biophysical tools we describe the ability of Nrp to function as a co-receptor for the VEGFR receptor tyrosine kinase. Two families of Nrp-1 ligands, Vascular Endothelial Growth Factor A (VEGF-A) and Semaphorin3F (Sema3F), physically compete for binding to the Nrp-1 b1 domain, and have opposite roles. VEGF-A is a potent pro-angiogenic cytokine while Sema3F is an angiogenesis inhibitor. Using coupled structural …

Heat Shock Protein 90 Inhibitors Prevent Lps-Induced Endothelial Barrier Dysfunction By Disrupting Rhoa Signaling, Atul D. Joshi, Christiana Dimitropoulou, Gagan S. Thangjam, Connie Snead, Sara Feldman, Nektarios Barabutis, David Fulton, Yali Hou, Sanjiv Kumar, Vijay Patel, Boris Gorshkov, Alexander D. Verin, Stephen M. Black, John D. Catravas

Bioelectrics Publications

Permeability of the endothelial monolayer is increased when exposed to the bacterial endotoxin LPS. Our previous studies have shown that heat shock protein (Hsp) 90 inhibitors protect and restore LPS-mediated hyperpermeability in bovine pulmonary arterial endothelial cells. In this study, we assessed the effect of Hsp90 inhibition against LPS-mediated hyperpermeability in cultured human lung microvascular endothelial cells (HLMVECs) and delineated the underlying molecular mechanisms. We demonstrate that Hsp90 inhibition is critical in the early phase, to prevent LPS-mediated hyperpermeability, and also in the later phase, to restore LPS-mediated hyperpermeability in HLMVECs. Because RhoA is a well known mediator of endothelial …

Dimethylarginine Dimethylaminohydrolase Ii Overexpression Attenuates Lps-Mediated Lung Leak In Acute Lung Injury, Saurabh Aggarwal, Christine M. Gross, Sanjiv Kumar, Christiana Dimitropoulou, Shruti Sharma, Boris A. Gorshkov, Supriya Sridhar, Qing Lu, Natalia V. Bogatcheva, Agnieszka J. Jezierska-Drutel, Rudolf Lucas, John D. Catravas, Stephen M. Black

Bioelectrics Publications

Acute lung injury (ALI) is a severe hypoxemic respiratory insufficiency associated with lung leak, diffuse alveolar damage, inflammation, and loss of lung function. Decreased dimethylaminohydrolase (DDAH) activity and increases in asymmetric dimethylarginine (ADMA), together with exaggerated oxidative/nitrative stress, contributes to the development of ALI in mice exposed to LPS. Whether restoring DDAH function and suppressing ADMA levels can effectively ameliorate vascular hyperpermeability and lung injury in ALI is unknown, and was the focus of this study. In human lung microvascular endothelial cells, DDAH II overexpression prevented the LPS-dependent increase in ADMA, superoxide, peroxynitrite, and protein nitration. DDAH II also attenuated …