scholarly journals Protective Effects and Mechanisms of Vaccarin on Vascular Endothelial Dysfunction in Diabetic Angiopathy

2019 ◽  
Vol 20 (18) ◽  
pp. 4587 ◽  
Author(s):  
Fei Xu ◽  
Yixiao Liu ◽  
Xuexue Zhu ◽  
Shuangshuang Li ◽  
Xuelin Shi ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Early Stage ◽  
Biological Activities ◽  
Vascular Endothelial Cell ◽  
Microvascular Endothelial Cell ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Compound C

Cardiovascular complications are a major leading cause of mortality in patients suffering from type 2 diabetes mellitus (T2DM). Vascular endothelial dysfunction is a core pathophysiological event in the early stage of T2DM and eventually leads to cardiovascular disease. Vaccarin (VAC), an active flavonoid glycoside extracted from vaccariae semen, exhibits extensive biological activities including vascular endothelial cell protection effects. However, little is known about whether VAC is involved in endothelial dysfunction regulation under high glucose (HG) or hyperglycemia conditions. Here, in an in vivo study, we found that VAC attenuated increased blood glucose, increased glucose and insulin tolerance, relieved the disorder of lipid metabolism and oxidative stress, and improved endothelium-dependent vasorelaxation in STZ/HFD-induced T2DM mice. Furthermore, in cultured human microvascular endothelial cell-1 (HMEC-1) cells, we showed that pretreatment with VAC dose-dependently increased nitric oxide (NO) generation and the phosphorylation of eNOS under HG conditions. Mechanistically, VAC-treated HMEC-1 cells exhibited higher AMPK phosphorylation, which was attenuated by HG stimulation. Moreover, HG-triggered miRNA-34a upregulation was inhibited by VAC pretreatment, which is in accordance with pretreatment with AMPK inhibitor compound C (CC). In addition, both reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) and VAC abolished HG-evoked dephosphorylation of AMPK and eNOS, increased miRNA-34a expression, and decreased NO production. These results suggest that VAC impedes HG-induced endothelial dysfunction via inhibition of the ROS/AMPK/miRNA-34a/eNOS signaling cascade.

scholarly journals Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function

2017 ◽  
Vol 313 (5) ◽  
pp. H890-H895 ◽  
Author(s):  
Matthew J. Rossman ◽  
Rachelle E. Kaplon ◽  
Sierra D. Hill ◽  
Molly N. McNamara ◽  
Jessica R. Santos-Parker ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cell Senescence ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Healthy Humans ◽  
Age Related ◽  
Habitual Exercise

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r = −0.49, P = 0.003), p21 ( r = −0.38, P = 0.03), and p16 ( r = −0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-exercise-and-endothelial-cell-senescence/ .

scholarly journals Angiotensin II-induced vascular endothelial dysfunction through RhoA/Rho kinase/p38 mitogen-activated protein kinase/arginase pathway

2011 ◽  
Vol 300 (5) ◽  
pp. C1181-C1192 ◽  
Author(s):  
Alia Shatanawi ◽  
Maritza J. Romero ◽  
Jennifer A. Iddings ◽  
Surabhi Chandra ◽  
Nagavedi S. Umapathy ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
P38 Mapk ◽  
Gene Knockout ◽  
Rho Kinase ◽  
Arginase Activity ◽  
No Production ◽  
Vascular Endothelial ◽  
Ang Ii ◽  
Vascular Endothelial Dysfunction

Enhanced vascular arginase activity impairs endothelium-dependent vasorelaxation by decreasing l-arginine availability to endothelial nitric oxide (NO) synthase, thereby reducing NO production. Elevated angiotensin II (ANG II) is a key component of endothelial dysfunction in many cardiovascular diseases and has been linked to elevated arginase activity. We determined signaling mechanisms by which ANG II increases endothelial arginase function. Results show that ANG II (0.1 μM, 24 h) elevates arginase activity and arginase I expression in bovine aortic endothelial cells (BAECs) and decreases NO production. These effects are prevented by the arginase inhibitor BEC (100 μM). Blockade of ANG II AT1 receptors or transfection with small interfering RNA (siRNA) for Gα12 and Gα13 also prevents ANG II-induced elevation of arginase activity, but siRNA for Gαq does not. ANG II also elevates active RhoA levels and induces phosphorylation of p38 MAPK. Inhibitors of RhoA activation (simvastatin, 0.1 μM) or Rho kinase (ROCK) (Y-27632, 10 μM; H1152, 0.5 μM) block both ANG II-induced elevation of arginase activity and phosphorylation of p38 MAPK. Furthermore, pretreatment of BAECs with p38 inhibitor SB-202190 (2 μM) or transfection with p38 MAPK siRNA prevents ANG II-induced increased arginase activity/expression and maintains NO production. Additionally, inhibitors of p38 MAPK (SB-203580, 5 μg·kg−1·day−1) or arginase (ABH, 8 mg·kg−1·day−1) or arginase gene knockout in mice prevents ANG II-induced vascular endothelial dysfunction and associated enhancement of arginase. These results indicate that ANG II increases endothelial arginase activity/expression through Gα12/13 G proteins coupled to AT1 receptors and subsequent activation of RhoA/ROCK/p38 MAPK pathways leading to endothelial dysfunction.

Abstract 310: ROS Induced Mitochondrioal Dysfunction Causes Endothelial Dyfunction by Downregulation Of SIRT1

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Cuk Seong Kim ◽  
Su-jung Choi ◽  
Harsha Nagar ◽  
Shuyu Piao ◽  
Seonhee Kim ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Mitochondrial Dysfunction ◽  
Vascular Disease ◽  
Vascular Endothelial Cell ◽  
Mitochondrial Morphology ◽  
Pathophysiological Mechanism ◽  
Vascular Endothelial ◽  
Down Regulation ◽  
Knock Out

Mitochondrial dysfunction has emerged as the major contributing factor in endothelial dysfunction and vascular disease. However, the key mechanism of mitochondrial dysfunction induced endothelial dysfunction has not to be clear identified. To determine whether mitochondrial dysfunction in endothelial cells play a key role in vascular disease, the phenotype of endothelial specific CRIF1 knock out (Crif1 -/- ) mouse and pathophysiological mechanism in vitro were examined. Crif1 -/- mouse showed a lower body weight and cardiac hypertrophy. Down-regulation of CRIF1 in vascular endothelial cell caused disturbances in the mitochondrial OXPHOS (oxidative phosphorylation) complexes, mitochondrial morphology as well as function leading to an increased mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP). In addition, down-regulation of CRIF1 also caused a decrease in Sirt1 expression along with increased eNOS acetylation leading to reduce NO production. Similar results were obtained in in vivo studies using the mouse with CRIF1-deficient vascular endothelial cell. Importantly, endothelium dependent vasorelaxation (EDR) of aortic rings from CRIF1 knock out mouse was considerably less as compared to the wild type counterparts. Also, the EDR was partially recovered following the adSirt1 treated aortic rings from mouse with Crif1-deficient vascular endothelial cell. Taken together, these findings indicate that CRIF1 plays an important role in the maintenance of mitochondrial function and endothelial function via the SIRT1-eNOS pathway.

scholarly journals Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Andrea Leiva ◽  
Bárbara Fuenzalida ◽  
Francisco Westermeier ◽  
Fernando Toledo ◽  
Carlos Salomón ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Cholesterol ◽  
Maternal Plasma ◽  
No Synthase ◽  
Plasma Cholesterol Level ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Potential Link ◽  
Available Information

Maternal physiological hypercholesterolemia occurs during pregnancy, ensuring normal fetal development. In some cases, the maternal plasma cholesterol level increases to above this physiological range, leading to maternal supraphysiological hypercholesterolemia (MSPH). This condition results in endothelial dysfunction and atherosclerosis in the fetal and placental vasculature. The fetal and placental endothelial dysfunction is related to alterations in the L-arginine/nitric oxide (NO) pathway and the arginase/urea pathway and results in reduced NO production. The level of tetrahydrobiopterin (BH4), a cofactor for endothelial NO synthase (eNOS), is reduced in nonpregnant women who have hypercholesterolemia, which favors the generation of the superoxide anion rather than NO (from eNOS), causing endothelial dysfunction. However, it is unknown whether MSPH is associated with changes in the level or metabolism of BH4; as a result, eNOS function is not well understood. This review summarizes the available information on the potential link between MSPH and BH4in causing human fetoplacental vascular endothelial dysfunction, which may be crucial for understanding the deleterious effects of MSPH on fetal growth and development.

Effect of angiotensin(1-7) on the expression of E-selectin induced by angiotensinII and its mechanism in vascular endothelial cell

2010 ◽  
Vol 34 (8) ◽  
pp. S71-S71
Author(s):  
Xiaohui Shen ◽  
Zhi‑Bin Wen ◽  
Na Li ◽  
Qingmei Cheng ◽  
Xiaofan He ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial

Alterations in Vascular Endothelial Cell-related Plasma Proteins In Thalassaemic Patients and their Correlation with Clinical Symptoms

1995 ◽  
Vol 74 (04) ◽  
pp. 1045-1049 ◽  
Author(s):  
P Butthep ◽  
A Bunyaratvej ◽  
Y Funahara ◽  
H Kitaguchi ◽  
S Fucharoen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Immunosorbent Assay ◽  
Plasma Proteins ◽  
Clinical Symptoms ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Enzyme Linked Immunosorbent Assay ◽  
Vascular Endothelial ◽  
Leg Ulcers

SummaryAn increased level of plasma thrombomodulin (TM) in α- and β- thalassaemia was demonstrated using an enzyme-linked immunosorbent assay (ELISA). Nonsplenectomized patients with β-thalassaemia/ haemoglobin E (BE) had higher levels of TM than splenectomized cases (BE-S). Patients with leg ulcers (BE-LU) were found to have the highest increase in TM level. Appearance of larger platelets in all types of thalassaemic blood was observed indicating an increase in the number of younger platelets. These data indicate that injury of vascular endothelial cells is present in thalassaemic patients.

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