Rocha Natalia P, Cleary Courtney, Colpo Gabriela D, Furr Stimming Erin, Teixeira Antonio L
The Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States.
HDSA Center of Excellence at The University of Texas Health Science Center at Houston, Houston, TX, United States.
Front Neurosci. 2020 Dec 18;14:594945. doi: 10.3389/fnins.2020.594945. eCollection 2020.
The renin-angiotensin system (RAS) has proven to be involved in the pathophysiology of neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease (AD), serving as a potential therapeutic target and a disease burden marker. Studies have associated negative clinical outcomes with the activation of the classical RAS arm composed of the angiotensin-converting enzyme (ACE) and angiotensin (Ang) II, while suggested positive outcomes with the activation of the counter-regulatory RAS arm involving ACE2 and Ang-(1-7). Huntington's disease (HD) shares many pathological and clinical outcomes with AD and PD, but the evidence of direct involvement of RAS components in the pathophysiology of HD is still limited and needs further investigation. Herein, we investigated peripheral levels of the RAS components Ang II, Ang-(1-7), ACE, and ACE2 in controls, premanifest, and manifest HD gene carriers and their relationship with clinical outcomes. Peripheral blood samples were collected via phlebotomy, and plasma concentrations of RAS components were measured by Enzyme-Linked Immunosorbent Assay. Clinical evaluation included a questionnaire about socio-demographic characteristics, motor, and cognitive assessments. Results showed (1) no significant group differences in plasma concentrations of RAS components; (2) positive correlations between ACE2 and Verbal Fluency Test (VFT) scores; and (3) negative correlations between Ang II and Mini-Mental State Examination scores. These results corroborate the proposed balance between the classical (ACE/Ang II) and the counter-regulatory [ACE2/Ang-(1-7)] arms of the RAS, with the former associated with negative clinical outcomes and the latter with positive effects in HD.
肾素-血管紧张素系统（RAS）已被证明参与神经退行性疾病的病理生理学过程，如帕金森病（PD）和阿尔茨海默病（AD），是一个潜在的治疗靶点和疾病负担标志物。研究表明，由血管紧张素转换酶（ACE）和血管紧张素（Ang）II组成的经典RAS分支的激活与不良临床结局相关，而涉及ACE2和Ang-（1-7）的反调节RAS分支的激活则提示有良好结局。亨廷顿舞蹈病（HD）与AD和PD有许多共同的病理和临床特征，但RAS成分直接参与HD病理生理学的证据仍然有限，需要进一步研究。在此，我们调查了对照组、HD基因携带者前驱期和发病期的RAS成分Ang II、Ang-（1-7）、ACE和ACE2的外周水平，以及它们与临床结局的关系。通过静脉穿刺采集外周血样本，采用酶联免疫吸附测定法测量RAS成分的血浆浓度。临床评估包括一份关于社会人口学特征、运动和认知评估的问卷。结果显示：（1）RAS成分的血浆浓度在各组间无显著差异；（2）ACE2与语言流畅性测试（VFT）得分呈正相关；（3）Ang II与简易精神状态检查表得分呈负相关。这些结果证实了RAS经典分支（ACE/Ang II）和反调节分支[ACE2/Ang-（1-7）]之间的平衡，前者与不良临床结局相关，后者在HD中具有积极作用。
