Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
Int J Mol Sci. 2024 Oct 29;25(21):11599. doi: 10.3390/ijms252111599.
Hypertension has been a threat to the health of people, the mechanism of which, however, remains poorly understood. It is clinically related to loss of nephron function, glomerular sclerosis, or necrosis, resulting in renal functional declines. The mechanisms underlying hypertension's development and progression to organ damage, including hypertensive renal damage, remain to be fully elucidated. As a developing approach, epigenetics has been postulated to elucidate the phenomena that otherwise cannot be explained by genetic studies. The main epigenetic hallmarks, such as DNA methylation, histone acetylation, deacetylation, noncoding RNAs, and protein N-homocysteinylation have been linked with hypertension. In addition to contributing to endothelial dysfunction and oxidative stress, biologically active gases, including NO, CO, and HS, are crucial regulators contributing to vascular remodeling since their complex interplay conducts homeostatic functions in the renovascular system. Importantly, epigenetic modifications also directly contribute to the pathogenesis of kidney damage via protein N-homocysteinylation. Hence, epigenetic modulation to intervene in renovascular damage is a potential therapeutic approach to treat renal disease and dysfunction. This review illustrates some of the epigenetic hallmarks and their mediators, which have the ability to diminish the injury triggered by hypertension and renal disease. In the end, we provide potential therapeutic possibilities to treat renovascular diseases in hypertension.
高血压一直威胁着人们的健康，但其中的发病机制仍知之甚少。它与肾单位功能丧失、肾小球硬化或坏死有关，导致肾功能下降。高血压的发展机制及其进展为器官损伤，包括高血压肾损伤的机制仍未完全阐明。作为一种新兴的研究方法，表观遗传学被认为可以阐明遗传研究无法解释的现象。主要的表观遗传标志，如 DNA 甲基化、组蛋白乙酰化、去乙酰化、非编码 RNA 和蛋白质 N-同型半胱氨酸化，与高血压有关。除了导致内皮功能障碍和氧化应激外，生物活性气体，包括 NO、CO 和 HS，作为血管重塑的重要调节因子，其复杂的相互作用在肾血管系统中发挥着维持体内平衡的功能。重要的是，表观遗传修饰也通过蛋白质 N-同型半胱氨酸化直接导致肾脏损伤的发病机制。因此，表观遗传调节干预肾血管损伤是治疗肾脏疾病和功能障碍的一种潜在治疗方法。本文综述了一些表观遗传标志及其介导因子，它们具有减轻高血压和肾脏疾病引起的损伤的能力。最后，我们提供了治疗高血压肾血管疾病的潜在治疗可能性。
