缺氧与泛血管疾病:探讨血管平滑肌细胞的缺氧诱导因子在泛血管病变中的作用

Hypoxia and panvascular diseases:exploring the role of hypoxia-inducible factors in vascular smooth muscle cells under panvascular pathologies

作为新兴的概念,泛血管疾病是一组心血管疾病,其主要特征是动脉粥样硬化,涉及心脏、脑、肾脏、四肢等重要器官.缺氧诱导因子(HIF)是心血管系统应对最常见应激(如缺氧)的主要调控因子.而血管平滑肌细胞(VSMC)是调节心血管系统压力和氧气输送的关键细胞.这两者的可塑性、多面性以及与泛血管疾病的相互作用值得深入研究.在泛血管疾病的病理状态下,过度活跃的VSMC(如动脉粥样硬化、肺动脉高压)或功能障碍的VSMC(如动脉瘤、血管钙化)与HIF密切相关.这些广泛存在的全身性疾病也突显了泛血管医学的跨学科性质.此外,考虑到VSMC与癌细胞的类似增殖特征,以及血管生成和癌症进展之间微妙的平衡,迫切需要更准确的调节靶点或联合用药方法,以增强HIF靶向治疗的有效性.基于以上内容,本文重点讨论了HIF信号通路在与VSMC相关的泛血管疾病中综合考虑整体与局部、时间与空间平衡的重要性,并探讨了在权衡利弊的情况下,HIF相关药物所对应的靶点对泛血管疾病的意义.

As an emerging discipline,panvascular diseases are a set of vascular diseases with atherosclerosis as the common pathogenic hallmark,which mostly affect vital organs like the heart,brain,kidney,and limbs.As the major responser to the most common stressor in the vasculature(hypoxia)—hypoxia-inducible factors(HIFs),and the primary regulator of pressure and oxygen delivery in the vasculature—vascular smooth muscle cells(VSMCs),their own multifaceted nature and their interactions with each other are fascinating.Abnormally active VSMCs(e.g.,atherosclerosis,pulmonary hypertension)or abnormally dysfunctional VSMCs(e.g.,aneurysms,vascular calcification)are associated with HIFs.These widespread systemic diseases also reflect the interdisciplinary nature of panvascular medicine.Moreover,given the comparable proliferative characteristics exhibited by VSMCs and cancer cells,and the delicate equilibrium between angiogenesis and cancer progression,there is a pressing need for more accurate modulation targets or combination approaches to bolster the effectiveness of HIF targeting therapies.Based on the aforementioned content,this review primarily focused on the significance of integrating the overall and local perspectives,as well as temporal and spatial balance,in the context of the HIF signaling pathway in VSMC-related panvascular diseases.Furthermore,the review discussed the implications of HIFtargeting drugs on panvascular disorders,while considering the trade-offs involved.