Abstract WMP78: The Efficacy of Angiotensin II Peptide Vaccination Against White Matter Lesions of Vascular Dementia in Rats

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Kouji Wakayama ◽  
Munehisa Shimamura ◽  
Hironori Nakagami ◽  
Ryuichi Morishita
Keyword(s):  
Endothelial Cells ◽  
Cognitive Function ◽  
Angiotensin Ii ◽  
White Matter ◽  
Western Blot ◽  
Vascular Dementia ◽  
White Matter Lesions ◽  
Ang Ii ◽  
Peptide Vaccination ◽  
Brdu Assay

Background & Purposes: There had been no attempt to show the efficacy of therapeutic vaccination in vascular dementia. A rat model of vascular dementia was prepared by bilateral common carotid artery ligation (2VO). The purpose of this study is to investigate whether pre-exposure Angiotensin II (Ang II) peptide vaccination exhibits the protective effects against white matter lesions (WML) in 2VO rats. Methods: After subcutaneous injection of Ang II peptide vaccine (10μg/200μl) or saline (200μl) to Wistar rats (male) at the time point of 6, 8 and 10 week-old, 2VO or sham surgery was performed at 12 week-old. Cognitive function was evaluated after 14 days of 2VO using the novel object recognition (NOR) test. Anti-Ang II antibody (Ab) level was quantified using ELISA. Histological examinations of WML and demyelination in the corpus callosum (CC) were evaluated using immunohistochemistry (IHC), 5-bromodeoxyuridine (BrdU) assay and Klüver-Barrera staining. Western blot analyses of VCAM-1, FGF2, phospho-CREB and CREB using proteins extracted from CC were performed to investigate the mechanism of restoration of WML by Ang II vaccination. Results: Histological examinations presented that exacerbation of WML and demyelination observed in saline treated (S) rats was ameliorated in Ang II vaccinated (V) rats. The results of NOR test indicated that cognitive dysfunction observed in S rats was improved in V rats at 14 days after 2VO. Expression of VCAM-1 in CC of S rats was significantly reduced in V rats at 7 days after 2VO. BrdU assay exhibited that vaccination accelerated the differentiation of oligodendrocyte progenitor cells (OPCs) in WML from 14 days to 28 days of 2VO. Western blot presented that both CREB phosphorylation and FGF2 expression in CC were increased in V rats compared with S rats at 14 days after 2VO. Double IHC showed that FGF2 expressing cells were mostly endothelial cells and astrocytes in WML. Conclusions: Ang II vaccination restored WML as well as cognitive function in 2VO rats. Our findings suggested that Ang II vaccination ameliorated cerebrovascular endothelial dysfunction which could accelerate the OPCs differentiation through increased expression of FGF2 in endothelial cells or astrocytes in 2VO rats.

scholarly journals Alpha-Asarone Protects Endothelial Cells from Injury by Angiotensin II

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-Xia Shi ◽  
Jiajun Yang ◽  
Tao Yang ◽  
Yong-Liang Xue ◽  
Jun Liu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Cell Injury ◽  
Fluorescent Dyes ◽  
Umbilical Vein ◽  
Protective Effects ◽  
Ang Ii ◽  
Versus Model

α-Asarone is the major therapeutical constituent ofAcorus tatarinowiiSchott. In this study, the potential protective effects ofα-asarone against endothelial cell injury induced by angiotensin II were investigatedin vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated withα-asarone (10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) atSer1177was determined by Western blotting.α-Asarone dose-dependently mitigated the Ang II-induced intracellular NO reduction (P<0.01versus model) and ROS production (P<0.01versus model). Furthermore, eNOS phosphorylation (Ser1177) by acetylcholine was significantly inhibited by Ang II, while pretreatment for 1 h withα-asarone partially prevented this effect (P<0.05versus model). Additionally, cell viability determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (105~114.5% versus control,P>0.05) was not affected after 24 h of incubation withα-asarone at 1–100 µmol/L. Therefore,α-asarone protects against Ang II-mediated damage of endothelial cells and may be developed to prevent injury to cardiovascular tissues.

scholarly journals Skeletal muscle-endothelial cell cross talk through angiotensin II

2010 ◽  
Vol 299 (6) ◽  
pp. C1402-C1408 ◽  
Author(s):  
Leeann M. Bellamy ◽  
Adam P. W. Johnston ◽  
Michael De Lisio ◽  
Gianni Parise
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Branch Point ◽  
Endothelial Cell Migration ◽  
Tube Length ◽  
Ang Ii

The role of angiotensin II (ANG II) in postnatal vasculogenesis and angiogenesis during skeletal muscle (SKM) regeneration is unknown. We examined the capacity of ANG II to stimulate capillary formation and growth during cardiotoxin-induced muscle regeneration in ACE inhibitor-treated ANG II type 1a receptor knockout (AT1a−/−) and C57Bl/6 control mice. Analysis of tibialis anterior (TA) cross-sections revealed 17% and 23% reductions in capillarization in AT1a−/− and captopril treated mice, respectively, when compared with controls, 21 days postinjury. Conversely, no differences in capillarization were detected at early time points (7 and 10 days). These results identify ANG II as a regulator of angiogenesis but not vasculogenesis in vivo. In vitro angiogenesis assays of human umbilical vein endothelial cells (HUVECs) further confirmed ANG II as proangiogeneic as 71% and 124% increases in tube length and branch point number were observed following ANG II treatment. Importantly, treatment of HUVECs with conditioned media from differentiated muscle cells resulted in an 84% and 203% increase in tube length and branch point number compared with controls, which was abolished following pretreatment of the cells with an angiotensin-converting enzyme inhibitor. The pro-angiogenic effect of ANG II can be attributed to an enhanced endothelial cell migration because both transwell and under agarose migration assays revealed a 37% and 101% increase in cell motility, respectively. Collectively, these data highlight ANG II as a proangiogenic regulator during SKM regeneration in vivo and more importantly demonstrates that ANG II released from SKM can signal endothelial cells and regulate angiogenesis through the induction of endothelial cell migration.

Cerebral White Matter Lesions have Low Impact on Cognitive Function in a Large Elderly Memory Clinic Population

2018 ◽  
Vol 63 (3) ◽  
pp. 1129-1139 ◽  
Author(s):  
Jules J. Claus ◽  
Mirthe Coenen ◽  
Salka S. Staekenborg ◽  
Jacqueline Schuur ◽  
Caroline E.M. Tielkes ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
White Matter Lesions ◽  
Cerebral White Matter ◽  
Memory Clinic ◽  
Cerebral White Matter Lesions ◽  
Clinic Population

Forget About It

2016 ◽  
Author(s):  
Ji Y. Chong ◽  
Michael P. Lerario
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Vascular Dementia ◽  
Clinical Course ◽  
White Matter Lesions ◽  
Acetylcholinesterase Inhibitors ◽  
Cognitive Symptoms ◽  
Vascular Events ◽  
Off Label

Cognitive impairment is common following stroke. The clinical course and presentation are variable in vascular dementia, but the diagnosis can often be tied to recent vascular events or to progressive white matter lesions on MRI. Because there is considerable overlap between patients with vascular and Alzheimer’s type dementia, both acetylcholinesterase inhibitors and memantine have been tried off-label to treat the cognitive symptoms of vascular dementia with mixed results.

White matter lesions, cerebral inflammation and cognitive function in a mouse model of cerebral hypoperfusion

2019 ◽  
Vol 1711 ◽  
pp. 193-201 ◽  
Author(s):  
Hagar Ben-Ari ◽  
Tzuri Lifschytz ◽  
Gilly Wolf ◽  
Amihai Rigbi ◽  
Tamar Blumenfeld-Katzir ◽  
...  
Keyword(s):  
Cognitive Function ◽  
White Matter ◽  
Mouse Model ◽  
White Matter Lesions ◽  
Cerebral Hypoperfusion ◽  
Cerebral Inflammation

scholarly journals Human glomerular endothelium: interplay among glucose, free fatty acids, angiotensin II, and oxidative stress

2010 ◽  
Vol 298 (1) ◽  
pp. F125-F132 ◽  
Author(s):  
Edgar A. Jaimes ◽  
Ping Hua ◽  
Run-Xia Tian ◽  
Leopoldo Raij
Keyword(s):  
Fatty Acids ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Free Fatty Acids ◽  
High Glucose ◽  
Renin Angiotensin System ◽  
Macrovascular Disease ◽  
Ang Ii ◽  
Cox 2

Glomerular endothelial cells (GEC) are strategically situated within the capillary loop and adjacent to the glomerular mesangium. GEC serve as targets of metabolic, biochemical, and hemodynamic signals that regulate the glomerular microcirculation. Unequivocally, hyperglycemia, hypertension, and the local renin-angiotensin system partake in the initiation and progression of diabetic nephropathy (DN). Whether free fatty acids (FFA) and reactive oxygen species (ROS) that have been associated with the endothelial dysfunction of diabetic macrovascular disease also contribute to DN is not known. Since endothelial cells from different organs and from different species may display different phenotypes, we employed human GEC to investigate the effect of high glucose (22.5 mmol/l), FFA (800 μmol/l), and angiotensin II (ANG II; 10−7 mol/l) on the genesis of ROS and their effects on endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX-2), and the synthesis of prostaglandins (PGs). We demonstrated that high glucose but not high FFA increased the expression of a dysfunctional eNOS as well as increased ROS from NADPH oxidase (100%) and likely from uncoupled eNOS. ANG II also induced ROS from NADPH oxidase. High glucose and ANG II upregulated (100%) COX-2 via ROS and significantly increased the synthesis of prostacyclin (PGI2) by 300%. In contrast, FFA did not upregulate COX-2 but increased PGI2 (500%). These novel studies are the first in human GEC that characterize the differential role of FFA, hyperglycemia, and ANG II on the genesis of ROS, COX-2, and PGs and their interplay in the early stages of hyperglcyemia.

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