Associations of the Angiotensin II Type 1 Receptor A
            1166
            C and the Endothelial NO Synthase G
            894
            T Gene Polymorphisms With Silent Subcortical White Matter Lesions in Essential Hypertension

Introduction: Hypertension is a complex disease in which a significant interaction between genetic and environmental factors takes place. The renin–angiotensin system plays an important role regulating blood pressure to maintain homeostasis and vascular tone. In the present work, the role of angiotensin II type 1-receptor (AGTR1) gene polymorphisms as susceptibility markers for hypertension was evaluated. Materials and methods: Five polymorphisms in the AGTR1 gene were genotyped by 5′ exonuclease TaqMan genotyping assays in 239 hypertensive and 371 non-hypertensive individuals. Results: A similar distribution of rs275651, rs275652, rs275653, and rs5183 polymorphisms was observed in both studied groups. Different distribution of rs5182 genotypes was observed between the studied groups ( p = 0.016). According to the co-dominant model, individuals with rs5182 CC genotype have a 1.83-fold increased risk of developing hypertension ( p = 0.009). Polymorphisms were distributed in two blocks: block 1 included the rs275651, rs275652, and rs275653 polymorphisms, whereas block 2 included the rs5183 and rs5182 polymorphisms. Individuals with hypertension showed increased frequency of ‘ CA’ haplotype of block 2 when compared to non-hypertensive individuals ( p = 0.015, odds ratio = 1.33). Conclusion: The results suggest that the rs5182 gene polymorphism could be involved in the risk of developing hypertension in Mexican individuals.

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

Stroke ◽

10.1161/str.51.suppl_1.wmp78 ◽

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.

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