Asante Isaac, Lu Angela, Mitchell Brooks I, Boisvert William A, Shikuma Cecilia M, Chow Dominic C, Louie Stan G
Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Alfred Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Metabolites. 2022 Dec 31;13(1):61. doi: 10.3390/metabo13010061.
Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin−angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals (n = 71, age > 40 years, stable ART > 3 months with HIV viral load < 50 copies/mL) were compared to a similar HIV seronegative group (n = 72). High-resolution B-mode ultrasound images of the right carotid bifurcation (RBIF) and right common carotid artery (RCCA) were conducted to measure the extent of carotid atherosclerotic vascular disease. Plasma RAS peptide levels were quantified using a liquid chromatography-mass spectrometry-based metabolomics assay. RAS peptide concentrations were compared between persons with HIV and persons without HIV, correlating their association with clinical and cardiac measures. Median precursor peptides (Ang(1-12) and AngI) were significantly higher in the HIV-positive group compared to the HIV-negative. Analyses of the patient subgroup not on antihypertensive medication revealed circulating levels of AngII to be four-fold higher in the HIV-positive subgroup. AngII and TNF-alpha levels were found to have a positive association with RCCA, and AngI/Ang(1-12) ratio and TNF-alpha levels were found to have a positive association with RBIF. In both predictive models, AngIII had a negative association with either RCCA or RBIF, which may be attributed to its ability to bind onto AT2R and thus oppose pro-inflammatory events. These results reveal systemic alterations in RAS as a result of chronic HIV infection, which may lead to the activation of inflammatory pathways associated with carotid thickening. RAS peptide levels and cytokine markers were associated with RCCA and RBIF measurements.
长期以来，慢性HIV感染一直与心血管疾病风险增加相关。肾素-血管紧张素系统（RAS）的代谢产物，如血管紧张素II（AngII），在调节血压和流体动力学方面发挥着重要作用。将HIV阳性个体（n = 71，年龄> 40岁，接受抗逆转录病毒治疗（ART）稳定> 3个月，HIV病毒载量< 50拷贝/mL）与类似的HIV血清阴性组（n = 72）进行横断面分析。对右颈动脉分叉（RBIF）和右颈总动脉（RCCA）进行高分辨率B型超声成像，以测量颈动脉粥样硬化血管疾病的程度。使用基于液相色谱-质谱的代谢组学分析法定量血浆RAS肽水平。比较HIV感染者和未感染者之间的RAS肽浓度，并将其与临床和心脏指标的关联进行相关性分析。与HIV阴性组相比，HIV阳性组的中值前体肽（Ang(1-12)和AngI）显著更高。对未服用抗高血压药物的患者亚组分析显示，HIV阳性亚组中AngII的循环水平高出四倍。发现AngII和肿瘤坏死因子-α（TNF-α）水平与RCCA呈正相关，AngI/Ang(1-12)比值和TNF-α水平与RBIF呈正相关。在两个预测模型中，AngIII与RCCA或RBIF均呈负相关，这可能归因于其与血管紧张素2型受体（AT2R）结合并因此对抗促炎事件的能力。这些结果揭示了慢性HIV感染导致的RAS系统性改变，这可能导致与颈动脉增厚相关的炎症途径激活。RAS肽水平和细胞因子标志物与RCCA和RBIF测量值相关。
