Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, China.
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, China.
Front Immunol. 2024 Mar 7;15:1335519. doi: 10.3389/fimmu.2024.1335519. eCollection 2024.
Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.
心血管疾病(CVDs)是一种多因素的慢性疾病,在全球范围内具有最高的发病率和死亡率。泛素-蛋白酶体系统(UPS)在蛋白质的翻译后修饰和质量控制中发挥着关键作用,通过降解错误折叠、半衰期短或无功能的调节蛋白来维持细胞内的稳态。非编码 RNA(ncRNA,如 microRNAs、长非编码 RNA、环状 RNA 和小干扰 RNA)作为表观遗传因子,直接或间接地参与各种生理和病理过程。调节泛素化或受 UPS 调节的 ncRNA 参与靶蛋白稳定性的执行。UPS、ncRNA 和 CVDs 之间的交联关系引起了研究人员的关注。在此,我们提供了 UPS 和 ncRNA 相互作用如何影响 CVDs 病理机制的最新研究进展和观点的更新,特别是心肌缺血/再灌注损伤、心肌梗死、心肌病、心力衰竭、动脉粥样硬化、高血压和缺血性中风。此外,我们进一步设想针对 UPS 的 RNA 干扰或 ncRNA 模拟物或抑制剂可能潜在地用作治疗工具和策略。