Center for Translational and Experimental Cardiology (CTEC), Zurich University Hospital, University of Zurich, 8952 Schlieren, Switzerland.
Health Science Interdisciplinary Center, Scuola Superiore Sant'Anna, 56127 Pisa, Italy.
Int J Mol Sci. 2023 Mar 2;24(5):4854. doi: 10.3390/ijms24054854.
Systemic arterial hypertension (AH) is a multifaceted disease characterized by accelerated vascular aging and high cardiometabolic morbidity and mortality. Despite extensive work in the field, the pathogenesis of AH is still incompletely understood, and its treatment remains challenging. Recent evidence has shown a deep involvement of epigenetic signals in the regulation of transcriptional programs underpinning maladaptive vascular remodeling, sympathetic activation and cardiometabolic alterations, all factors predisposing to AH. After occurring, these epigenetic changes have a long-lasting effect on gene dysregulation and do not seem to be reversible upon intensive treatment or the control of cardiovascular risk factors. Among the factors involved in arterial hypertension, microvascular dysfunction plays a central role. This review will focus on the emerging role of epigenetic changes in hypertensive-related microvascular disease, including the different cell types and tissues (endothelial cells, vascular smooth muscle cells and perivascular adipose tissue) as well as the involvement of mechanical/hemodynamic factors, namely, shear stress.
系统性动脉高血压(AH)是一种多方面的疾病,其特征是血管加速老化以及心血管代谢发病率和死亡率高。尽管该领域进行了广泛的研究,但 AH 的发病机制仍不完全清楚,其治疗仍然具有挑战性。最近的证据表明,表观遗传信号在调节导致血管重构不良、交感神经激活和心血管代谢改变的转录程序中深度参与,所有这些因素都容易导致 AH。这些表观遗传变化发生后,对基因失调具有持久的影响,并且似乎不会在强化治疗或控制心血管危险因素后逆转。在与动脉高血压相关的因素中,微血管功能障碍起着核心作用。本综述将重点介绍表观遗传变化在高血压相关微血管疾病中的新作用,包括不同的细胞类型和组织(内皮细胞、血管平滑肌细胞和血管周围脂肪组织)以及机械/血流动力学因素(即切应力)的参与。