van Deventer Cynthia A, Lindeque Jeremie Z, van Rensburg Peet J Jansen, Malan Leoné, van der Westhuizen Francois H, Louw Roan
Centre for Human Metabonomics, North-West University, Potchefstroom Campus, Potchefstroom, South Africa.
Hypertension in Africa Research Team (HART), North-West University, Potchefstroom Campus, Potchefstroom, South Africa.
J Am Soc Hypertens. 2015 Feb;9(2):104-14. doi: 10.1016/j.jash.2014.11.007. Epub 2014 Dec 3.
There is concern about the increasing burden of essential hypertension in urban-dwelling black South Africans, especially males. Several studies have investigated urbanization and hypertension in South Africans, but in-depth metabolomics studies on these urbanized hypertensives are still lacking. We aimed to investigate hypertension via two metabolomics methods in order to explore underlying biological mechanisms, demonstrating the effectiveness of these methods in cardiovascular research. A comprehensive characterization of a group (n = 25) of black male South Africans was performed using urinary gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry metabolic profiling in conjunction with 24-hour ambulatory blood pressure readings and anthropometric, clinical, and biochemical markers. Average 24-hour blood pressure readings served as the grouping variable, and test subjects were divided into quintiles. Statistical analyses were performed on Quintile 1 (normotensive subjects) and Quintile 5 (extreme hypertensive subjects). After feature selection was performed, several metabolites and cardiometabolic risk markers, including abdominal obesity and markers of liver damage, inflammation, and oxidative stress were significantly perturbed in Quintile 5 (hypertensives) compared with Quintile 1 (P < .05). Pathway analysis revealed perturbations in several systems involved in ethanol metabolism via shifted global NADH/NAD(+) ratio. Although alcohol abuse has been established as a risk factor for hypertension, this study illustrated a metabolic perturbation associated with alcohol abuse, contributing to the development of hypertension-possibly by altering bioenergetics through a shift in the NADH/NAD(+) ratio. Following this finding, future intervention studies on alcohol moderation, as well as further enhancement of metabolomics methods in cardiovascular research are highly recommended.
南非城市黑人，尤其是男性，原发性高血压负担日益加重，令人担忧。已有多项研究调查了南非人的城市化与高血压情况，但针对这些城市化高血压患者的深入代谢组学研究仍很缺乏。我们旨在通过两种代谢组学方法研究高血压，以探索潜在的生物学机制，证明这些方法在心血管研究中的有效性。我们对一组（n = 25）南非黑人男性进行了全面表征，采用尿气相色谱 - 质谱联用和液相色谱 - 质谱联用代谢谱分析，并结合24小时动态血压读数以及人体测量、临床和生化指标。平均24小时血压读数作为分组变量，受试对象被分为五等份。对第一组（血压正常受试者）和第五组（极度高血压受试者）进行了统计分析。在进行特征选择后，与第一组相比，第五组（高血压患者）中包括腹型肥胖以及肝损伤、炎症和氧化应激标志物在内的几种代谢物和心脏代谢风险标志物受到了显著干扰（P < 0.05）。通路分析显示，由于整体NADH/NAD(+)比值的改变，参与乙醇代谢的几个系统受到了干扰。虽然酗酒已被确认为高血压的一个危险因素，但本研究揭示了一种与酗酒相关的代谢紊乱，可能通过改变NADH/NAD(+)比值来改变生物能量学，从而导致高血压的发生。基于这一发现，强烈建议未来开展关于适度饮酒的干预研究，以及进一步改进心血管研究中的代谢组学方法。
