Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952, Schlieren, Switzerland.
First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
Basic Res Cardiol. 2021 Mar 26;116(1):23. doi: 10.1007/s00395-021-00863-x.
Despite major advances in prevention and treatment, cardiac and cerebral atherothrombotic complications still account for substantial morbidity and mortality worldwide. In this context, inflammation is involved in the chronic process leading atherosclerotic plaque formation and its complications, as well as in the maladaptive response to acute ischemic events. For this reason, modulation of inflammation is nowadays seen as a promising therapeutic strategy to counteract the burden of cardio- and cerebrovascular disease. Being produced and recognized by both inflammatory and vascular cells, the complex network of cytokines holds key functions in the crosstalk of these two systems and orchestrates the progression of atherothrombosis. By binding to membrane receptors, these soluble mediators trigger specific intracellular signaling pathways eventually leading to the activation of transcription factors and a deep modulation of cell function. Both stimulatory and inhibitory cytokines have been described and progressively reported as markers of disease or interesting therapeutic targets in the cardiovascular field. Nevertheless, cytokine inhibition is burdened by harmful side effects that will most likely prevent its chronic use in favor of acute administrations in well-selected subjects at high risk. Here, we summarize the current state of knowledge regarding the modulatory role of cytokines on atherosclerosis, myocardial infarction, and stroke. Then, we discuss evidence from clinical trials specifically targeting cytokines and the potential implication of these advances into daily clinical practice.
尽管在预防和治疗方面取得了重大进展，但心脏和脑动脉粥样血栓并发症仍在全球范围内造成大量发病率和死亡率。在这种情况下，炎症参与了导致动脉粥样硬化斑块形成及其并发症的慢性过程，以及对急性缺血事件的适应性反应。因此，炎症调节被认为是一种有前途的治疗策略，可用于对抗心血管疾病的负担。细胞因子的复杂网络由炎症细胞和血管细胞产生并识别，在这两个系统的串扰中具有关键功能，并协调动脉粥样血栓形成的进展。这些可溶性介质通过与膜受体结合，触发特定的细胞内信号通路，最终导致转录因子的激活和细胞功能的深度调节。刺激和抑制细胞因子都已被描述，并逐渐被报道为心血管领域疾病的标志物或有趣的治疗靶点。然而，细胞因子抑制存在有害的副作用，这很可能阻止其在高风险的精选人群中进行慢性使用，而倾向于在急性情况下使用。在这里，我们总结了细胞因子在动脉粥样硬化、心肌梗死和中风中的调节作用的最新知识状态。然后，我们讨论了专门针对细胞因子的临床试验的证据，以及这些进展对日常临床实践的潜在影响。
