scholarly journals Ubiquinol Supplementation Improves Gender-Dependent Cerebral Vasoreactivity and Ameliorates Chronic Inflammation and Endothelial Dysfunction in Patients with Mild Cognitive Impairment

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 143
Author(s):  
Sonia García-Carpintero ◽  
Javier Domínguez-Bértalo ◽  
Cristina Pedrero-Prieto ◽  
Javier Frontiñán-Rubio ◽  
Mariano Amo-Salas ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Vascular Dysfunction ◽  
Transcranial Doppler Sonography ◽  
Endothelial Damage ◽  
Microvascular Endothelial Cell ◽  
Neurological Improvement ◽  
Male Patients ◽  
Cerebral Vasoreactivity

Ubiquinol can protect endothelial cells from multiple mechanisms that cause endothelial damage and vascular dysfunction, thus contributing to dementia. A total of 69 participants diagnosed with mild cognitive impairment (MCI) received either 200 mg/day ubiquinol (Ub) or placebo for 1 year. Cognitive assessment of patients was performed at baseline and after 1 year of follow-up. Patients’ cerebral vasoreactivity was examined using transcranial Doppler sonography, and levels of Ub and lipopolysaccharide (LPS) in plasma samples were quantified. Cell viability and necrotic cell death were determined using the microvascular endothelial cell line bEnd3. Coenzyme Q10 (CoQ) levels increased in patients supplemented for 1 year with ubiquinol versus baseline and the placebo group, although higher levels were observed in male patients. The higher cCoQ concentration in male patients improved cerebral vasoreactivity CRV and reduced inflammation, although the effect of Ub supplementation on neurological improvement was negligible in this study. Furthermore, plasma from Ub-supplemented patients improved the viability of endothelial cells, although only in T2DM and hypertensive patients. This suggests that ubiquinol supplementation could be recommended to reach a concentration of 5 μg/mL in plasma in MCI patients as a complement to conventional treatment.

Abstract P097: Molecular Mechanisms of VEGFR Inhibition-induced Endothelial Cell Damage

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Francisco J Rios ◽  
Augusto C Montezano ◽  
Lucas Van Der Mey ◽  
Heather Y Small ◽  
Carmine Savoia ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Mrna Levels ◽  
Ang Ii ◽  
Vegf Inhibitors

VEGF/VEGFR inhibitors, used as anti-angiogenic drugs to treat cancer, induce severe hypertension. Molecular mechanisms whereby VEGF inhibitors cause hypertension are unclear, but nitric oxide (NO) and oxidative stress may be involved. We questioned whether reactive oxygen species (ROS) and Ang II, important regulators of vascular function in hypertension, also play a role in VEGF inhibitor-induced vascular dysfunction. Human microvascular endothelial cells (HMECs) were stimulated with vatalanib (VAT-VEGFR inhibitor) and gefitinib (GEF-EGFR inhibitor) in the absence/presence of Ang II. Activation of eNOS and MAPKs were assessed by immunoblotting. Antioxidant enzyme mRNA was analysed by qPCR. Microparticle levels were measured by flow cytometry. Endothelial microparticles, biomarkers of endothelial damage, tend to increase in subjects treated with VEGFR inhibitors. Phosphorylation of eNOS activation site (Ser1177) (28.3% ± 7.1) was decreased by VAT, while no changes were observed after exposure of HMECs to GEF (p<0.05). VAT decreased mRNA expression of Nox4 (0.5 ± 0.2) and H2O2-regulating antioxidants enzymes such as catalase (0.4 ± 0.1) and glutathione peroxidase (0.4 ± 0.1), while increased mRNA levels of Nox5 (3.35±1.1) (p<0.05 vs. veh). Ang II stimulation increased eNOS (171.2% ± 17.4) and ERK1/2 (177.5% ± 38.5) activation (p<0.05); all effects were blocked only by GEF. Inhibition of VEGFR also blocked Ang II effects on SOD1 (1.33 ± 0.1), HO-1 (1.6 ± 0.3) and NQO1 (1.6 ± 0.3) mRNA levels (p<0.05). In addition, Ang II increased Nox4 mRNA expression through VEGFR-dependent mechanisms. VEGFR1/2 and AT2R, but not AT1R, were expressed in HMEC. Ang II effects on eNOS phosphorylation were inhibited by PD123319 (AT2R antagonist) but not by losartan (AT1R antagonist). In conclusion, our data identify novel mechanisms whereby AngII, possibly through AT2R-dependent VEGFR transactivation, regulates eNOS activation, MAPK signalling and H2O2-related antioxidant enzymes. In addition to changes in NO availability, VEGFR inhibition may interfere with the redox status of endothelial cells, leading to vascular dysfunction and hypertension.

scholarly journals Circulating Endothelial Cells and Chronic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kunying Zhang ◽  
Fang Yin ◽  
Lin Lin
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Endothelial dysfunction may play a crucial role in initiation of the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CEC) have been developed as a novel marker of endothelial function. We describe, in great detail, mechanisms of endothelial dysfunction and CEC detachment. We also review the relationship between numbers of CEC and disease severity and response to treatment. In addition, we describe the possible clinical use of CEC in chronic kidney disease (CKD) and kidney transplantation. In summary, CEC have been developed as a novel approach to assess the endothelial damage. Measurement of the CEC level would provide an important diagnostic and prognostic value on the endothelium status and the long-term outcome of vascular dysfunction.

scholarly journals RELATION BETWEEN ERECTILE DYSFUNCTION AND AMNESTIC MILD COGNITIVE IMPAIRMENT ACROSS TWO TIME POINTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S958-S958
Author(s):  
Richard Vandiver ◽  
Michael J Lyons ◽  
Kristy Cuthbert
Keyword(s):  
Erectile Dysfunction ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Functioning ◽  
Vascular Dysfunction ◽  
Amnestic Mild Cognitive Impairment ◽  
Us Military ◽  
Amnestic Mci ◽  
Common Etiology ◽  
The Relationship

Abstract Previous research by the Vietnam Era Twin Study of Aging (VETSA) demonstrated an association between erectile dysfunction (ED) and cognitive functioning. That finding supports a hypothesis that cardiovascular dysfunction may underlie both ED and problems in cognitive functioning. The purpose of the current research was to extend these findings by investigating a putative association between ED and amnestic and non-amnestic mild cognitive impairment (MCI). MCI is of particular interest because of its relationship with Alzheimer’s disease and other dementing illnesses. VETSA is a longitudinal study of twins who served in the US military during the Vietnam conflict (N= 960) consisting of data collected at age 20 (enlistment), age 55 (VETSA 1), and 61 (VETSA 2). The results of the current analyses show that ED is related to both amnestic MCI (p=.032) and non-amnestic MCI (p=.009) at VETSA 1. At VETSA 2, however, the relationship between ED and non-amnestic MCI was no longer significant (p=.751) while the relationship between ED and amnestic MCI was stronger (p=.001). These results are consistent with ED and MCI sharing, to some extent, a common etiology. Vascular dysfunction, which is associated with both ED and MCI, is a plausible mechanism responsible for the observed relationship. These results also highlight the potential role that may be played by ED as an early indicator of cognitive impairment and, perhaps, pre-symptomatic AD.

P1.09 MILD COGNITIVE IMPAIRMENT IS ASSOCIATED WITH SYSTEMIC VASCULAR DYSFUNCTION

2013 ◽  
Vol 7 (3-4) ◽  
pp. 113
Author(s):  
R.M. Bruno ◽  
L. Ghiadoni ◽  
F. Stea ◽  
F. Faita ◽  
S. Taddei ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Vascular Dysfunction

Mild cognitive impairment is associated with systemic vascular dysfunction

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1140-P1140
Author(s):  
R. M. Bruno ◽  
L. Ghiadoni ◽  
S. Taddei ◽  
F. Stea ◽  
F. Faita ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Vascular Dysfunction
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