Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance (MHA), Berlin, Germany.
Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance (MHA), Berlin, Germany.
Atherosclerosis. 2023 Jun;374:34-43. doi: 10.1016/j.atherosclerosis.2022.11.021. Epub 2022 Dec 6.
Despite extraordinary advances in the comprehension of the pathophysiology of atherosclerosis and the employment of very effective treatments, cardiovascular diseases are still a major cause of mortality and represent a large share of health expenditure worldwide. Atherosclerosis is a disease affecting the medium and large arteries, which consists of a progressive accumulation of fatty substances, cellular waste products and fibrous elements, which culminates in the buildup of a plaque obstructing the blood flow. Endothelial dysfunction represents an early pathological event, favoring immune cells recruitment and triggering local inflammation. The release of inflammatory cytokines and other signaling molecules stimulates phenotypic modifications in the underlying vascular smooth muscle cells, which, in physiological conditions, are responsible for the maintenance of vessels architecture while regulating vascular tone. Vascular smooth muscle cells are highly plastic and may respond to disease stimuli by de-differentiating and losing their contractility, while increasing their synthetic, proliferative, and migratory capacity. This phenotypic switching is considered a pathological hallmark of atherogenesis and is ruled by the activation of selective gene programs. The advent of genomics and the improvement of sequencing technologies deepened our knowledge of the complex gene expression regulatory networks mediated by non-coding RNAs, and favored the rise of innovative therapeutic approaches targeting the non-coding transcriptome. In the context of atherosclerosis, long non-coding RNAs have received increasing attention as potential translational targets, due to their contribution to the molecular dynamics modulating the expression of vascular smooth muscle cells contractile/synthetic gene programs. In this review, we will focus on the most well-characterized long non-coding RNAs contributing to atherosclerosis by controlling expression of the contractile apparatus and genes activated in perturbed vascular smooth muscle cells.
尽管在理解动脉粥样硬化的病理生理学方面取得了非凡的进展，并采用了非常有效的治疗方法，但心血管疾病仍然是全球死亡率的主要原因，也是全球卫生支出的重要组成部分。动脉粥样硬化是一种影响大中动脉的疾病，它由脂肪物质、细胞废物和纤维元素的逐渐积累组成，最终导致斑块堆积，阻碍血液流动。内皮功能障碍是一种早期的病理事件，有利于免疫细胞的募集，并引发局部炎症。炎症细胞因子和其他信号分子的释放刺激了血管平滑肌细胞的表型改变，在生理条件下，血管平滑肌细胞负责维持血管结构，同时调节血管张力。血管平滑肌细胞具有高度的可塑性，可能会对疾病刺激作出反应，去分化并失去收缩性，同时增加其合成、增殖和迁移能力。这种表型转换被认为是动脉粥样硬化发生的病理标志，由特定基因程序的激活所控制。基因组学的出现和测序技术的改进加深了我们对非编码 RNA 介导的复杂基因表达调控网络的认识，并促进了针对非编码转录组的创新治疗方法的兴起。在动脉粥样硬化的背景下，长非编码 RNA 因其对调节血管平滑肌细胞收缩/合成基因程序的分子动力学的贡献而受到越来越多的关注，成为潜在的转化治疗靶点。在这篇综述中，我们将重点关注通过控制血管平滑肌细胞收缩装置和受干扰的血管平滑肌细胞中激活基因的表达来促进动脉粥样硬化的最具特征性的长非编码 RNA。
