Why the study?
Whether the protective effects of remote ischemic preconditioning and prolyl 4-hydroxylase inhibition against ischemia/reperfusion-induced cardiac injury are synergetic remained to be elucidated.
Does the combination of remote ischemic preconditioning and prolyl 4-hydroxylase inhibition reduce ischemia/reperfusion-induced cardiac injury in a rabbit model?
Does the combination of remote ischemic preconditioning and prolyl 4-hydroxylase inhibition reduce ischemia/reperfusion-induced cardiac injury in a rabbit model?
The combination of remote ischemic preconditioning and PHD inhibition synergistically protects against myocardial ischemia/reperfusion injury in a rabbit model.
Supports combined RIP and PHD inhibition in experimental I/R models; leaves open clinical translation for cardioprotection.
It has been reported that hypoxia‑inducible factor 1α (HIF‑1α) serves a key role in the protective effect of remote ischemic preconditioning (RIP) in ischemia/reperfusion (I/R)‑induced cardiac injury. Moreover, inhibition of prolyl 4‑hydroxylase (PHD), an enzyme responsible for HIF‑1α degradation, prevents I/R‑induced cardiac injury. However, whether their protective effects are synergetic remains to be elucidated. The present study aimed to investigate the protective effect of RIP, PHD inhibition using dimethyloxalylglycine (DMOG) and their combination on I/R‑induced cardiac injury. Rabbits were randomly divided into seven groups: i) Sham; ii) I/R; iii) lung RIP + I/R; iv) thigh RIP + I/R; v) DMOG + I/R; vi) DMOG + lung RIP + I/R; and vii) DMOG + thigh RIP + I/R. I/R models were established via 30 min left coronary artery occlusion and 3 h reperfusion. For lung/thigh RIP, rabbits received left pulmonary artery (or left limb) ischemia for 25 min and followed by release for 5 min. Some rabbits were administered 20 mg/kg DMOG. The results demonstrated that both lung/thigh RIP and DMOG significantly decreased myocardial infarct size, creatine kinase activity and myocardial apoptosis in I/R rabbits. Furthermore, the combination of RIP and PHD inhibition exerted synergetic protective effects on these aforementioned changes. The mechanistic study indicated that both treatments increased mRNA and protein expression levels of HIF‑1α and its downstream regulators, including vascular endothelial growth factor (VEGF), AKT and endothelial nitric oxide synthase (eNOS). In conclusion, the present study demonstrated that RIP and PHD inhibition exerted synergetic protective effects on cardiac injury via activation of HIF‑1α and the downstream VEGF/AKT‑eNOS signaling pathway.
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Yang et al. (2022) studied this question.
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