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

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 dys-functional VSMCs (e.g., aneurysms, vascular calcification) are associated with HIFs. These widespread sys-temic diseases also reflect the interdisciplinary nature of panvascular medicine. Moreover, given the comparable proliferative characteristics exhibited by VSMCs and cancer cells, and the delicate equilib-rium between angiogenesis and cancer progression, there is a pressing need for more accurate modula-tion 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 path-way in VSMC-related panvascular diseases. Furthermore, the review discussed the implications of HIF-targeting drugs on panvascular disorders, while considering the trade-offs involved.& COPY; 2023 Science China Press. Published by Elsevier B.V. and Science China Press. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).