A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates.

A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates. Am J Physiol Heart Circ Physiol. 2021 Jan 22;: Authors: Shimatani K, Sato H, Saito A, Sasai M, Watanabe K, Mizukami K, Kamohara M, Miyagawa S, Sawa Y Abstract Critical limb ischemia (CLI) is a severe state of peripheral artery disease with high unmet clinical needs. Further, there are no effective treatment options for CLI patients. Based on preclinical study results, predicting the clinical efficacy of CLI treatments is typically difficult because conventional hindlimb ischemia (HLI) rodent models display spontaneous recovery from ischemia, which is not observed in CLI patients. Therefore, we aimed to develop a novel chronic and severe HLI model to properly evaluate the therapeutic effects of drug candidates for CLI. Severe HLI mice (Type-N) were generated by increasing the excised area of blood vessels in a hindlimb of NOG mice. We selected chronic Type-N mice without spontaneous recovery of blood flow based on the number of necrotic nails and blood flow rate at 2 weeks after surgery. Immunohistochemistry and gene expression analysis at 9 weeks after the Type-N operation revealed that the ischemic limb was in a steady state with impaired angiogenesis, like that observed in CLI patients. Therapeutic treatment with cilostazol, which is used for intermittent claudication, did not restore blood flow in chronic Type-N mice. In c...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research