Targeted Delivery of Genes to Endothelial Cells and Cell- and Gene-Based Therapy in Pulmonary Vascular Diseases

2013 ◽  
pp. 1749-1779 ◽  
Author(s):  
Colin M. Suen ◽  
Shirley H.J. Mei ◽  
Lakshmi Kugathasan ◽  
Duncan J. Stewart
Keyword(s):  
Endothelial Cells ◽  
Targeted Delivery ◽  
Vascular Diseases ◽  
Pulmonary Vascular Diseases

scholarly journals Incremental Experience in In Vitro Primary Culture of Human Pulmonary Arterial Endothelial Cells Harvested from Swan-Ganz Pulmonary Arterial Catheters

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3229
Author(s):  
Birger Tielemans ◽  
Leanda Stoian ◽  
Allard Wagenaar ◽  
Mathias Leys ◽  
Catharina Belge ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Diseases ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Endothelial Phenotype ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells ◽  
Pulmonary Vascular Diseases

Pulmonary arterial hypertension (PAH) is a devastating condition affecting the pulmonary microvascular wall and endothelium, resulting in their partial or total obstruction. Despite a combination of expensive vasodilatory therapies, mortality remains high. Personalized therapeutic approaches, based on access to patient material to unravel patient specificities, could move the field forward. An innovative technique involving harvesting pulmonary arterial endothelial cells (PAECs) at the time of diagnosis was recently described. The aim of the present study was to fine-tune the initial technique and to phenotype the evolution of PAECs in vitro subcultures. PAECs were harvested from Swan-Ganz pulmonary arterial catheters during routine diagnostic or follow up right heart catheterization. Collected PAECs were phenotyped by flow cytometry and immunofluorescence focusing on endothelial-specific markers. We highlight the ability to harvest patients’ PAECs and to maintain them for up to 7–12 subcultures. By tracking the endothelial phenotype, we observed that PAECs could maintain an endothelial phenotype for several weeks in culture. The present study highlights the unique opportunity to obtain homogeneous subcultures of primary PAECs from patients at diagnosis and follow-up. In addition, it opens promising perspectives regarding tailored precision medicine for patients suffering from rare pulmonary vascular diseases.

PERSPECTIVES OF APPLICATION OF ANTIBODIES AGAINST ENDOGLIN (CD105) FOR VISUALIZATION AND ANTI-ANGIOGENE THERAPY OF TUMORS

2018 ◽  
Vol 64 (4) ◽  
pp. 504-507
Author(s):  
Vladimir Klimovich ◽  
Natalya Vartanyan ◽  
Anastasiya Stolbovaya ◽  
Lidiya Terekhina ◽  
Olga Shashkova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Human Plasma ◽  
Vascular Endothelium ◽  
Immune Complexes ◽  
Targeted Delivery ◽  
Biological Fluids ◽  
Therapeutic Drugs ◽  
Cultured Endothelial Cells ◽  
Hybridoma Technology

During last years monoclonal antibodies (MAB) directed against vascular endothelium markers demonstrated their efficiency for visualization and targeted delivery of therapeutic drugs to tumors. Endoglin (CD105) which serves as a key element that determines endothelial cells quiescence or activation is one of such markers. Endoglin is highly expressed on the vascular endothelium of growing tumors. A first panel of MAB against endoglin in our country was produced at the hybridoma technology laboratory of RRC RST named after A.M. Granov. On the basis of these MAB ELISA was created allowing detection of endoglin in human plasma and other biological fluids. Several MAB had been shown to bind endoglin on the membrane of the cultured endothelial cells and to persist there for several hours. During the first 30 min after binding some of the immune complexes “endoglin-MAB” were internalized into the cytoplasm and were found included in the endosomes. In future these MAB can be used to create the reagents for the addressed delivery of isotope tags both on the membrane and into the cytoplasm of endothelial cells.

scholarly journals Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases

2018 ◽  
Vol 20 (1) ◽  
pp. 78 ◽  
Author(s):  
Huiju Lee ◽  
Yoon Choi
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Neurovascular Unit ◽  
Vascular Diseases ◽  
Cell Types ◽  
Cns Injury ◽  
Perivascular Cells ◽  
Major Barrier ◽  
The Central Nervous System

Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders. CNS injury elicits responses from activated glia (e.g., astrocytes, oligodendrocytes, and microglia) and from damaged perivascular cells (e.g., pericytes and endothelial cells). Most brain lesions cause extensive proliferation and growth of existing glial cells around the site of injury, leading to reactions causing glial scarring, which may act as a major barrier to neuronal regrowth in the CNS. In addition, damaged perivascular cells lead to the breakdown of the blood-neural barrier, and an increase in immune activation, activated glia, and neuroinflammation. The present review discusses the regenerative role of HO metabolites, such as CO and BR, in various vascular diseases of the CNS such as stroke, traumatic brain injury, diabetic retinopathy, and Alzheimer’s disease, and the role of several other signaling molecules.

scholarly journals TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells

2018 ◽  
Vol 19 (11) ◽  
pp. 3428 ◽  
Author(s):  
Hyun-Jung Choi ◽  
Na-Eun Kim ◽  
Byeong Kim ◽  
Miran Seo ◽  
Ji Heo
Keyword(s):  
Endothelial Cells ◽  
Rho Gtpases ◽  
Leukocyte Adhesion ◽  
Hippo Pathway ◽  
Specific Inhibitor ◽  
Vascular Diseases ◽  
Adhesive Properties ◽  
Sprouting Angiogenesis ◽  
Tnf Α

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

scholarly journals Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Histone Deacetylase ◽  
Proinflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
Transcriptional Level ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases.

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