Anwar M Akhtar, Saleh Alaaeldin I, Al Olabi Reem, Al Shehabi Tuqa S, Eid Ali H
Department of Biological and Environmental Sciences, Qatar University, Doha, Qatar.
Qatar Biomedical Research Institute, Doha, Qatar.
Vascul Pharmacol. 2016 Jul;82:41-50. doi: 10.1016/j.vph.2016.02.002. Epub 2016 Feb 20.
Hypertension is a predominant risk factor for cardiovascular diseases and a major health care burden. Accumulating epidemiological and experimental evidence suggest that adult-onset hypertension may have its origins during early development. Upon exposure to glucocorticoids, the fetus develops hypertension, and the offspring may be programmed to continue the hypertensive trajectory into adulthood. Elevated oxidative stress and deranged nitric oxide system are not only hallmarks of adult hypertension but are also observed earlier in life. Endothelial dysfunction and remodeling of the vasculature, which are robustly associated with increased incidence of hypertension, are likely to have been pre-programmed during fetal life. Apparently, genomic, non-genomic, and epigenomic factors play a significant role in the development of hypertension, including glucocorticoid-driven effects on blood pressure. In this review, we discuss the involvement of the aforementioned participants in the pathophysiology of hypertension and suggest therapeutic opportunities for targeting epigenome modifiers, potentially for personalized medicine.
高血压是心血管疾病的主要危险因素，也是一项重大的医疗负担。越来越多的流行病学和实验证据表明，成人期高血压可能起源于早期发育阶段。胎儿在接触糖皮质激素后会患上高血压，其后代可能会被设定沿着高血压轨迹发展至成年期。氧化应激升高和一氧化氮系统紊乱不仅是成人高血压的特征，在生命早期也能观察到。血管内皮功能障碍和血管重塑与高血压发病率增加密切相关，很可能在胎儿期就已预先设定。显然，基因组、非基因组和表观基因组因素在高血压的发生发展中起着重要作用，包括糖皮质激素对血压的驱动作用。在这篇综述中，我们讨论了上述因素在高血压病理生理学中的作用，并提出了针对表观基因组修饰剂的治疗机会，这可能为个性化医疗提供依据。
