Vitamin D and hypoxia-inducible factors signaling interplay: A hypothesis-driven review of therapeutic strategies for acute cerebral infarction.

Acute cerebral infarction (ACI) is a severe cerebrovascular disease characterized by a steadily rising global incidence rate, emerging as a leading cause of disability and mortality worldwide. Hypoxia-inducible factors (HIFs) play a pivotal role in the pathophysiological process of ACI. In recent years, mounting evidence has suggested a potential interplay between vitamin D (Vit D) and HIFs. Preclinical studies (e.g., rat cerebral ischemia models) have demonstrated that Vit D can stabilize HIF-1α, a key member of the HIFs family, which in turn reduces cerebral infarct volume by up to 50%. Clinical studies (patient cohort follow-ups) further reveal that ACI patients with Vit D-deficiency face a 30% higher risk of poor outcomes. Based on these findings, this review proposes a core hypothesis: Vit D exerts a neuroprotective effect in ACI by modulating HIFs’-related mechanisms, providing a novel direction for disease treatment. We speculate that for Vit D-deficient ACI patients, initiating supplementation therapy (e.g., 6000 IU/day) within 72 h ofn onset can reduce infarct volume by ≥ 40% by enhancing the protective effects of HIFs. In summary, the Vit D-HIFs axis is a highly promising therapeutic target for ACI, and future research should focus on validating this mechanism and promoting its clinical translation.