Ultrastructural changes in bovine pulmonary artery endothelial cells exposed to 80% O2 in vitro

In Vitro ◽  
1983 ◽  
Vol 19 (9) ◽  
pp. 714-722 ◽  
Author(s):  
Sheu-Ling Lee ◽  
William H. J. Douglas ◽  
Susan M. Deneke ◽  
Barry L. Fanburg
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Ultrastructural Changes

Ultrastructural changes of bovine pulmonary artery endothelial cells irradiated in vitro with a 137Cs source

1983 ◽  
Vol 15 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Sheu-Ling Lee ◽  
William H.J. Douglas ◽  
Peck-Sun Lin ◽  
Barry L Fanburg
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Ultrastructural Changes ◽  
137Cs Source

Beta3-adrenergic stimulation restores endothelial mitochondrial dynamics and prevents pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Oliver ◽  
S.F Rocha ◽  
M Spaczynska ◽  
D.V Lalama ◽  
M Gomez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Therapeutic Strategy ◽  
Mitochondrial Dynamics ◽  
Systolic Pressure ◽  
Funding Source ◽  
Pulmonary Arterial

Abstract Background Endothelial dysfunction is one of the most important hallmarks of pulmonary arterial hypertension (PAH). This leads to anomalous production of vasoactive mediators that are responsible for a higher vascular tone and a subsequent increase in pulmonary artery pressure (PAP), and to an increased vascular permeability that favors perivascular inflammation and remodeling, thus worsening the disease. Therefore, preservation of the endothelial barrier could become a relevant therapeutic strategy. Purpose In previous studies, others and we have suggested the pharmacological activation of the β3-adrenergic receptor (AR) as a potential therapeutic strategy for pulmonary hypertension (PH) due to left heart disease. However, its potential use in other forms of PH remain unclear. The aim of the present study was to elucidate whether the β3-AR agonist mirabegron could preserve pulmonary endothelium function and be a potential new therapy in PAH. Methods For this purpose, we have evaluated the effect of mirabegron (2 and 10 mg/kg·day) in different animal models, including the monocrotaline and the hypoxia-induced PAH models in rats and mice, respectively. Additionally, we have used a transgenic mouse model with endothelial overexpression of human β3-AR in a knockout background, and performed in vitro experiments with human pulmonary artery endothelial cells (HPAECs) for mechanistic experiments. Results Our results show a dose dependent effect of mirabegron in reducing mean PAP and Right Ventricular Systolic Pressure in both mice and rats. In addition, the use of transgenic mice has allowed us to determine that pulmonary endothelial cells are key mediators of the beneficial role of β3-AR pathway in ameliorating PAH. Mechanistically, we have shown in vitro that activation of β3-AR with mirabegron protects HPAECs from hypoxia-induced ROS production and mitochondrial fragmentation by restoring mitochondrial fission/fusion dynamics. Conclusions This protective effect of mirabegron would lead to endothelium integrity and preserved pulmonary endothelial function, which are necessary for a correct vasodilation, avoiding increased permeability and remodeling. Altogether, the current study demonstrates a beneficial effect of the β3-AR agonist mirabegron that could open new therapeutic avenues in PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Programa de Atracciόn de Talento, Comunidad de Madrid

High-pressure pulsation of central and microvessel pulmonary artery endothelial cells

1988 ◽  
Vol 254 (2) ◽  
pp. C338-C343 ◽  
Author(s):  
M. Rabinovitch ◽  
T. Bothwell ◽  
M. Mullen ◽  
B. N. Hayakawa
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Artery ◽  
Phase Contrast ◽  
Surface Characteristics ◽  
Cellular Damage ◽  
External Diameter ◽  
Microcarrier Beads ◽  
Central Pulmonary Artery ◽  
Quartz Transducer

We developed an in vitro method of pulsating central and microvessel pulmonary artery endothelial cells that would allow us to study the effects of increased distending pressures over a prolonged period of time. Preservation of the contact-inhibited monolayer was assessed on phase contrast microscopy and, in addition, scanning and transmission electron microscopy (SEM, TEM) were used to determine whether there were alterations in the surface characteristics or intracytoplasmic organelles that suggested cellular damage. The cells used were obtained from Rambouillet lambs, age 3-5 days, anesthetized with halothane and ventilated. The endothelium was harvested from the central pulmonary artery (CPA) by scraping the luminal surface and from the microvessels (MPA) by infusing microcarrier beads 40-140 microns external diameter. After the second passage in culture, the cells were seeded onto the translucent, flexible polyvinylchloride membrane of a transducer dome and grown to confluence. The cell dome was then connected to a blank dome with an attached quartz transducer, to a reservoir, and to stainless steel bellows tubing, all filled with culture medium and affixed to a pulsation generator. By varying the height of the reservoir, the amplitude of excursion of the bellows tubing, and the rate, the cells could be pulsated at a given distending pressure and frequency. Confluent CPA endothelial cells from three lambs and MPA cells from two others were studied after pulsation at both 100/60 and 20/10 mmHg, 60 times/min for 48 h and after nonpulsation. On phase contrast light microscopy and on SEM, the cells remained confluent.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Infection kinetics, prostacyclin release and cytokine-mediated modulation of the mechanism of cell death during bluetongue virus infection of cultured ovine and bovine pulmonary artery and lung microvascular endothelial cells

2001 ◽  
Vol 82 (4) ◽  
pp. 787-794 ◽  
Author(s):  
Christopher D. DeMaula ◽  
Mark A. Jutila ◽  
Dennis W. Wilson ◽  
N. James MacLachlan
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Pulmonary Artery ◽  
Bluetongue Virus ◽  
Infected Sheep ◽  
The Other ◽  
Microvascular Endothelial Cells ◽  
Bluetongue Disease ◽  
Haemorrhagic Disease

Bluetongue virus (BTV) infection causes a haemorrhagic disease in sheep, whereas BTV infection typically is asymptomatic in cattle. Injury to the endothelium of small blood vessels is responsible for the manifestations of disease in BTV-infected sheep. The lungs are central to the pathogenesis of BTV infection of ruminants; thus endothelial cells (ECs) cultured from the pulmonary artery and lung microvasculature of sheep and cattle were used to investigate the basis for the disparate expression of bluetongue disease in the two species. Ovine and bovine microvascular ECs infected at low multiplicity with partially purified BTV were equally susceptible to BTV-induced cell death, yet ovine microvascular ECs had a lower incidence of infection and produced significantly less virus than did bovine microvascular ECs. Importantly, the relative proportions of apoptotic and necrotic cells were significantly different in BTV-infected EC cultures depending on the species of EC origin and the presence of inflammatory mediators in the virus inoculum. Furthermore, BTV-infected ovine lung microvascular ECs released markedly less prostacyclin than the other types of ECs. Results of these in vitro studies are consistent with the marked pulmonary oedema and microvascular thrombosis that characterize bluetongue disease of sheep but which rarely, if ever, occur in BTV-infected cattle.

The injury effect of oxygen free radicals in vitro on cultured pulmonary artery endothelial cells from broilers

2007 ◽  
Vol 82 (3) ◽  
pp. 382-387 ◽  
Author(s):  
Jia-Qiang Pan ◽  
Jin-Chun Li ◽  
Xun Tan ◽  
Wei-Dong Sun ◽  
Jin-Yong Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Free Radicals ◽  
Pulmonary Artery ◽  
Oxygen Free Radicals ◽  
Effect Of Oxygen

scholarly journals Prostacyclin production in vitro by rabbit aortic endothelium: correction for unstirred diffusional layers

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1047-1052 ◽  
Author(s):  
EF Grabowski ◽  
GJ Naus ◽  
BB Weksler
Keyword(s):  
Endothelial Cells ◽  
Thrombin Generation ◽  
Ultrastructural Changes ◽  
Variable Degree ◽  
Transmission Electron ◽  
Endothelial Surface ◽  
Fluid Layers ◽  
Major Variable ◽  
Smooth Muscle Relaxant

Abstract The degree of mixing in fluid layers immediately adjacent to the endothelial surface is a major variable in assessment of prostacyclin (PGI2) production by cultured endothelial cells or intact vessel endothelium in vitro. Lack of adequate mixing should lead to underestimation of true production because PGI2 immediately adjacent to endothelium would be only poorly sampled upon buffer collection. Thoracic aortas from 38 New Zealand white rabbits were therefore excised, opened longitudinally, and mounted endothelial side uppermost in a buffer-filled chamber which excluded cut tissue edges from study. Production of PGI2 under unstirred and magnetically stirred conditions was measured by radioimmunoassay (RIA) for 6-keto-PGF1 alpha. For animals pretreated with the combination of papaverine and heparin (see below), unstimulated and arachidonate-stimulated 6-keto-PGF1 alpha increased with stirring rate toward limits of 2.9 and 28.5 ng/cm2/min, respectively. Unstimulated and stimulated 6-keto PGF1 alpha measured at 650 rpm, for example, were greater than their values at 0 rpm by factors of 3.5 (2P less than .01) and 3.7 (2P less than .001), respectively. The process of vessel excision, however, produces another variable: degree of injury to endothelium caused by such factors as secondary vessel contraction and thrombin generation. Vessel contraction and thrombin generation can be minimized, respectively, by the use of a smooth muscle relaxant and heparin administered prior to killing of the animals. The rabbits were, therefore, grouped according to intravenous (IV) treatment, prior to killing, with saline, papaverine (4 mg/kg), heparin (200 U/kg) or the combination of papaverine and heparin (same doses). As compared with pretreatment with saline, papaverine alone, or heparin alone, pretreatment with the combination of papaverine and saline led to increases in stimulated 6- keto-PGF1 alpha of 1.6- to 2.8-fold. By transmission electron microscopy, endothelium from animals pretreated with saline showed ultrastructural changes, including disruption of cytoplasm, separation without detachment of most endothelial cells from subendothelium, and focal areas of denudation. In contrast, ultrastructural integrity of endothelium was preserved in aortas of animals pretreated with combined papaverine and heparin. These results support the hypothesis that unstirred diffusional layers lead, in vitro, to underestimation of PGI2 production, especially when vessels are protected from excisional injury.(ABSTRACT TRUNCATED AT 400 WORDS)

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