Store-operated calcium entry promotes shape change in pulmonary endothelial cells expressing Trp1

1998 ◽  
Vol 275 (3) ◽  
pp. L574-L582 ◽  
Author(s):  
Timothy M. Moore ◽  
George H. Brough ◽  
Paul Babal ◽  
John J. Kelly ◽  
Ming Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Shape ◽  
Transient Receptor Potential ◽  
Shape Change ◽  
Filamentous Actin ◽  
Cell Shape Change ◽  
Pulmonary Endothelial Cells ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells

Activation of Ca2+ entry is known to produce endothelial cell shape change, leading to increased permeability, leukocyte migration, and initiation of angiogenesis in conduit-vessel endothelial cells. The mode of Ca2+ entry regulating cell shape is unknown. We hypothesized that activation of store-operated Ca2+ channels (SOCs) is sufficient to promote cell shape change necessary for these processes. SOC activation in rat pulmonary arterial endothelial cells increased free cytosolic Ca2+ that was dependent on a membrane current having a net inward component of 5.45 ± 0.90 pA/pF at −80 mV. Changes in endothelial cell shape accompanied SOC activation and were dependent on Ca2+ entry-induced reconfiguration of peripheral (cortical) filamentous actin (F-actin). Because the identity of pulmonary endothelial SOCs is unknown, but mammalian homologues of the Drosophila melanogaster transient receptor potential ( trp) gene have been proposed to form Ca2+ entry channels in nonexcitable cells, we performed RT-PCR using Trp oligonucleotide primers in both rat and human pulmonary arterial endothelial cells. Both cell types were found to express Trp1, but neither expressed Trp3 nor Trp6. Our study indicates that 1) Ca2+ entry in pulmonary endothelial cells through SOCs produces cell shape change that is dependent on site-specific rearrangement of the microfilamentous cytoskeleton and 2) Trp1 may be a component of pulmonary endothelial SOCs.

scholarly journals Gαq-TRPC6-mediated Ca2+Entry Induces RhoA Activation and Resultant Endothelial Cell Shape Change in Response to Thrombin

2006 ◽  
Vol 282 (11) ◽  
pp. 7833-7843 ◽  
Author(s):  
Itender Singh ◽  
Nebojsa Knezevic ◽  
Gias U. Ahmmed ◽  
Vidisha Kini ◽  
Asrar B. Malik ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Rhoa Activation ◽  
Cell Shape Change

Oxidant stress regulates basal endothelin-1 production by cultured rat pulmonary endothelial cells

1997 ◽  
Vol 273 (4) ◽  
pp. L768-L774 ◽  
Author(s):  
John R. Michael ◽  
Boaz A. Markewitz ◽  
Donald E. Kohan
Keyword(s):  
Endothelial Cells ◽  
Glucose Oxidase ◽  
Oxidant Stress ◽  
Iron Chelator ◽  
Leucine Incorporation ◽  
Endothelin 1 ◽  
Pulmonary Endothelial Cells ◽  
Pulmonary Arterial ◽  
Stress Influences ◽  
Arterial Endothelial Cells

Endothelin-1 (ET-1) is a pluripotent mediator that modulates vascular tone and influences the inflammatory response. Patients with inflammatory lung disorders frequently have elevated circulating ET-1 levels. Because these pathophysiological conditions generate reactive oxygen species that can regulate gene expression, we investigated whether the level of oxidant stress influences ET-1 production in cultured rat pulmonary arterial endothelial cells (RPAEC). Treatment with the antioxidant 1,3-dimethyl-2-thiourea (10 mM) or the iron chelator deferoxamine (1.8 μM) doubles basal ET-1 release. Conversely, exposing cells to H2O2generated by glucose and glucose oxidase (0.1–10 mU/ml) for 4 h causes a concentration-dependent decrease in ET-1 release. This effect occurs at concentrations of glucose oxidase that do not affect [3H]leucine incorporation or specific 51Cr release from RPAEC. Catalase prevents the decrease in ET-1 synthesis caused by glucose and glucose oxidase. Glucose and glucose oxidase decrease not only ET-1 generation but also ET-1 mRNA as assessed by semiquantitative polymerase chain reaction. Our results indicate that changes in oxidative stress can either up- or downregulate basal ET-1 generation by cultured pulmonary endothelial cells.

Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium

1987 ◽  
Vol 63 (5) ◽  
pp. 2159-2163 ◽  
Author(s):  
T. C. Rodell ◽  
J. C. Cheronis ◽  
C. L. Ohnemus ◽  
D. J. Piermattei ◽  
J. E. Repine
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Lung Injury ◽  
Xanthine Oxidase ◽  
Neutrophil Elastase ◽  
Superoxide Anion ◽  
Cell Monolayers ◽  
Pulmonary Arterial ◽  
Isolated Lungs ◽  
Arterial Endothelial Cells

Xanthine oxidase (XO)-generated toxic O2 metabolites appear to contribute to reperfusion injury, but the possibility that XO is involved in hyperoxic or neutrophil elastase-mediated injury has not been investigated. We found that lungs isolated from rats fed a tungsten-rich diet had negligible XO activities and after exposure to hyperoxia developed less acute edematous injury during perfusion with buffer or purified neutrophil elastase than XO-replete lungs from control rats which had been exposed to hyperoxia. In parallel, tungsten-treated XO-depleted cultured bovine pulmonary arterial endothelial cells made less superoxide anion and as monolayers leaked less 125I-labeled albumin after exposure to neutrophil elastase than XO-replete endothelial cell monolayers. Our findings suggest that XO-derived O2 metabolites contribute to acute edematous lung injury from hyperoxia directly and by enhancing susceptibility to neutrophil elastase.

scholarly journals Mechanism of endothelial cell shape change in oxidant injury

1989 ◽  
Vol 46 (4) ◽  
pp. 339-349 ◽  
Author(s):  
Daniel B. Hinshaw ◽  
Jeanne M. Burger ◽  
Barbara C. Armstrong ◽  
Paul A. Hyslop
Keyword(s):  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Oxidant Injury ◽  
Cell Shape Change

Endothelial cell phospholipid distribution and phospholipase activity during acute and chronic hypoxia

1993 ◽  
Vol 265 (3) ◽  
pp. C770-C780 ◽  
Author(s):  
A. V. Tretyakov ◽  
H. W. Farber
Keyword(s):  
Endothelial Cells ◽  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Endothelial Cell ◽  
Plasma Membranes ◽  
Chronic Hypoxia ◽  
Phospholipase Activity ◽  
Pulmonary Arterial ◽  
Phospholipid Distribution ◽  
Arterial Endothelial Cells

We have previously reported alterations in cyclooxygenase metabolism in cultured aortic and pulmonary arterial endothelial cells exposed to acute and chronic hypoxia. These alterations depended on the duration and degree of the hypoxic exposure, on the vascular bed from which the endothelial cells were derived, and possibly on the availability of arachidonic acid secondary to modifications in metabolic substrate, membrane phospholipids, and/or membrane phospholipase activity. To investigate this last point further, we have compared plasma membrane phospholipid distribution and phospholipase activity in cultured aortic and pulmonary arterial endothelial cells exposed to both acute and chronic hypoxia, using two different precursors (acetic acid and arachidonic acid) and three different membrane preparations (cell homogenates, partially purified plasma membranes, and highly purified plasma membranes). We found that exposure to acute and chronic hypoxia has profound and complicated effects on endothelial cell phospholipid composition and phospholipase activity and that these effects depend on the origin of the endothelial cells and the duration of hypoxia. Furthermore, we found that the alterations in endothelial cell phospholipid distribution in response to hypoxia depend on the purity of the plasma membrane preparation and the metabolic precursor used to study phospholipid metabolism. Finally, these studies suggested that alterations in phospholipids during hypoxia occurred to a greater extent in compartments of endothelial cells other than the plasma membranes and that the well-recognized tolerance of endothelial cells to hypoxia may be due, in part, to preservation of the integrity of their plasma membranes during exposure to acute and chronic hypoxia.

Caspase-4/11–Mediated Pulmonary Artery Endothelial Cell Pyroptosis Contributes to Pulmonary Arterial Hypertension

Hypertension ◽  
2022 ◽  
Author(s):  
Yusi Wu ◽  
Bingjie Pan ◽  
Zhen Zhang ◽  
Xiaohui Li ◽  
Yiping Leng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Vascular Remodeling ◽  
Endothelial Cell Function ◽  
Pulmonary Arterial ◽  
Arterial Endothelial Cells

Background: Endothelial dysfunction enhances vascular inflammation, which initiates pulmonary arterial hypertension (PAH) pathogenesis, further induces vascular remodeling and right ventricular failure. Activation of inflammatory caspases is an important initial event at the onset of pyroptosis. Studies have shown that caspase-1–mediated pyroptosis has played a crucial role in the pathogenesis of PAH. However, the role of caspase-11, another inflammatory caspase, remains to be elucidated. Therefore, the purpose of this study was to clarify the role of caspase-11 in the development of PAH and its mechanism on endothelial cell function. Methods: The role of caspase-11 in the progression of PAH and vascular remodeling was assessed in vivo. In vitro, the effect of caspase-4 silencing on the human pulmonary arterial endothelial cells pyroptosis was determined. Results: We confirmed that caspase-11 and its human homolog caspase-4 were activated in PAH animal models and TNF (tumor necrosis factor)-α–induced human pulmonary arterial endothelial cells. Caspase-11 −/− relieved right ventricular systolic pressure, right ventricle hypertrophy, and vascular remodeling in Sugen-5416 combined with chronic hypoxia mice model. Meanwhile, pharmacological inhibition of caspase-11 with wedelolactone exhibited alleviated development of PAH on the monocrotaline-induced rat model. Moreover, knockdown of caspase-4 repressed the onset of TNF-α–induced pyroptosis in human pulmonary arterial endothelial cells and inhibited the activation of pyroptosis effector GSDMD (gasdermin D) and GSDME (gasdermin E). Conclusions: These observations identified the critical role of caspase-4/11 in the pyroptosis pathway to modulate pulmonary vascular dysfunction and accelerate the progression of PAH. Our findings provide a potential diagnostic and therapeutic target in PAH.

Quantification of damage by air emboli to lung microvessels in anesthetized sheep

1984 ◽  
Vol 57 (5) ◽  
pp. 1360-1368 ◽  
Author(s):  
K. H. Albertine ◽  
J. P. Wiener-Kronish ◽  
K. Koike ◽  
N. C. Staub
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Close Contact ◽  
Air Bubbles ◽  
Pulmonary Arterial ◽  
Ultrastructural Damage ◽  
Air Embolus ◽  
Arterial Endothelial Cells ◽  
Lung Lymph ◽  
Lung Lymph Flow

We studied the ultrastructural damage caused by venous air embolization in anesthetized sheep by morphological techniques after monitoring hemodynamics and lymph dynamics. Lung lymph flow and protein flux increased during 1 and 4 h of venous air embolization, results consistent with increased microvascular permeability. Histologically, the air emboli were restricted to the small pulmonary arterial vessels (1,000 to 100 micron in diam). Neutrophils accumulated around the air bubbles and formed intravascular clumps. Ultrastructurally, at the air embolus-blood interface, neutrophils appeared attached to a layer a proteinaceous material. Many neutrophils were in close contact with the pulmonary arterial endothelial cells. We found gaps (0.1–3 micron in width) between the endothelial cells of the pulmonary arterial microvessels. Beneath these gaps the basal lamina was disrupted. Other vessel types were unaffected. Some lymphocytes were seen near the air bubbles and the endothelial cell gaps. Platelets remained discoid, and fibrin clots were not observed. These results indicate that venous air embolization in sheep damages the pulmonary arterial microvessels. Neutrophils are closely associated to both the air emboli and the endothelial cell gaps.

Regulation of endothelin-1 gene expression by cell shape and the microfilament network in vascular endothelium

1997 ◽  
Vol 273 (5) ◽  
pp. C1764-C1774 ◽  
Author(s):  
Adel Moussa Malek ◽  
Ike W. Lee ◽  
Seth L. Alper ◽  
Seigo Izumo
Keyword(s):  
Gene Expression ◽  
Endothelial Cell ◽  
Cell Shape ◽  
Shape Change ◽  
Cell Contact ◽  
Bovine Aortic Endothelial Cell ◽  
Mrna Levels ◽  
Endothelin 1 ◽  
Cell Shape Change ◽  
Dose Dependent

Endothelial synthesis and release of endothelin-1 (ET-1) are exquisitely regulated by external shear and strain. We tested the hypothesis that manipulation of endothelial cell shape can regulate ET-1 gene expression. Treatment of bovine aortic endothelial cell (BAEC) monolayers with cytochalasin D disrupted F-actin and induced cell retraction and rounding, in parallel with time- and dose-dependent specific decreases in ET-1 mRNA levels. Treatments with forskolin, phorbol 12-myristate 13-acetate, staurosporine, and genistein also induced cell shape change and decreased F-actin staining and ET-1 mRNA levels. BAEC plated onto nonadhesive petri dishes coated with decreasing concentrations of synthetic RGD polymer showed RGD dose-dependent decreases in cell spreading and in F-actin microfilament elaboration. These changes were specifically accompanied by decreases in ET-1 peptide secretion (60%) and, via posttranscriptional mechanisms, ET-1 mRNA (94%) and were not due to decreased cell-cell contact. We conclude that the shape and microfilament network of endothelial cells are potent posttranscriptional regulators of ET-1 gene expression.

Sign in / Sign up

Export Citation Format

Share Document