Department of Translational and Vascular Biology, University of Texas Health Sciences Center at Tyler, 11937 US Hwy 271, Tyler, TX, 75708, USA.
Curr Hypertens Rep. 2018 Feb 14;20(1):6. doi: 10.1007/s11906-018-0815-9.
Although the roles of oxidant stress and redox perturbations in hypertension have been the subject of several reviews, role of thioredoxin (Trx), a major cellular redox protein in age-related hypertension remains inadequately reviewed. The purpose of this review is to bring readers up-to-date with current understanding of the role of thioredoxin in age-related hypertension.
Age-related hypertension is a major underlying cause of several cardiovascular disorders, and therefore, intensive management of blood pressure is indicated in most patients with cardiovascular complications. Recent studies have shown that age-related hypertension was reversed and remained lowered for a prolonged period in mice with higher levels of human Trx (Trx-Tg). Additionally, injection of human recombinant Trx (rhTrx) decreased hypertension in aged wild-type mice that lasted for several days. Both Trx-Tg and aged wild-type mice injected with rhTrx were normotensive, showed increased NO production, decreased arterial stiffness, and increased vascular relaxation. These studies suggest that rhTrx could potentially be a therapeutic molecule to reverse age-related hypertension in humans. The reversal of age-related hypertension by restoring proteins that have undergone age-related modification is conceptually novel in the treatment of hypertension. Trx reverses age-related hypertension via maintaining vascular redox homeostasis, regenerating critical vasoregulatory proteins oxidized due to advancing age, and restoring native function of proteins that have undergone age-related modifications with loss-of function. Recent studies demonstrate that Trx is a promising molecule that may ameliorate or reverse age-related hypertension in older adults.
尽管氧化应激和氧化还原失调在高血压中的作用已经被多次综述，但在与年龄相关的高血压中，一种主要的细胞氧化还原蛋白——硫氧还蛋白（Trx）的作用仍未得到充分的研究。本综述的目的是使读者了解当前对 Trx 在与年龄相关的高血压中的作用的认识。
与年龄相关的高血压是几种心血管疾病的主要潜在原因，因此，大多数伴有心血管并发症的患者都需要积极控制血压。最近的研究表明，在 Trx 水平较高的小鼠中，与年龄相关的高血压得到逆转并持续降低，而且这种降低可以持续很长一段时间。此外，在年老的野生型小鼠中注射人重组 Trx（rhTrx）可以降低高血压，并且这种降压作用可以持续数天。注射 rhTrx 的 Trx-Tg 小鼠和年老的野生型小鼠均血压正常，一氧化氮（NO）生成增加，动脉僵硬减少，血管舒张增加。这些研究表明，rhTrx 可能是一种有潜力的治疗分子，可以逆转人类的与年龄相关的高血压。通过恢复因衰老而发生改变的蛋白质来逆转与年龄相关的高血压，这在高血压的治疗中是一个新概念。Trx 通过维持血管氧化还原平衡、还原因衰老而氧化的关键血管调节蛋白、以及恢复因衰老而发生功能丧失的蛋白质的天然功能来逆转与年龄相关的高血压。最近的研究表明，Trx 是一种有前途的分子，可能会改善或逆转老年人的与年龄相关的高血压。
