scholarly journals Blocking of VEGF-A is not sufficient to completely revert its long-term effects on the barrier formed by retinal endothelial cells

2022 ◽  
pp. 108945
Author(s):  
Heidrun L. Deissler ◽  
Matus Rehak ◽  
Catharina Busch ◽  
Armin Wolf
2003 ◽  
Vol 77 (5) ◽  
pp. 1220-1228 ◽  
Author(s):  
Fabio Pellegatta ◽  
Alberto AE Bertelli ◽  
Bart Staels ◽  
Christian Duhem ◽  
Alessandro Fulgenzi ◽  
...  

2021 ◽  
Vol 23 (1) ◽  
pp. 211
Author(s):  
Mikhail V. Samsonov ◽  
Nikita V. Podkuychenko ◽  
Asker Y. Khapchaev ◽  
Eugene E. Efremov ◽  
Elena V. Yanushevskaya ◽  
...  

Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.


Author(s):  
Clifton F. Frilot ◽  
Stephen R. Patton ◽  
Steven A. Jones

The fluid dynamic environment within an artery is an important contributor to haemostasis. Fluid mechanics can alter the biochemical environment through convection and diffusion of reactive substances. It can bring the platelets close to the wall through convection and enhanced diffusion, cause platelet activation through hemodynamic shear stresses, and alter the substrate for platelet adhesion through shear effects on endothelial cells. Shear produces long-term effects on endothelial cells, such as morphological changes in the cells and adaptation of the size of the artery. It can also affect endothelial cells in the short term by increasing calcium release or release of nitric oxide.


2020 ◽  
Vol 194 ◽  
pp. 108004 ◽  
Author(s):  
Heidrun L. Deissler ◽  
Jan-Niklas Stutzer ◽  
Gerhard K. Lang ◽  
Salvatore Grisanti ◽  
Gabriele E. Lang ◽  
...  

Author(s):  
T. M. Seed ◽  
M. H. Sanderson ◽  
D. L. Gutzeit ◽  
T. E. Fritz ◽  
D. V. Tolle ◽  
...  

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.


Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.


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