Hypoxia inducible factor-prolyl hydroxylase inhibitor ameliorates the myopathy in a mice model of chronic kidney disease.

Hypoxia inducible factor-prolyl hydroxylase inhibitor ameliorates the myopathy in a mice model of chronic kidney disease. Am J Physiol Renal Physiol. 2019 Oct 07;: Authors: Qian FY, Li ZL, Guo YD, Gao HC, Gu LH, Le K, Xie CM, Wang B, Zhang ZJ Abstract Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Pro-angiogenesis therapy is therefore considered a potentially effective strategy for limiting CKD-associated myopathy. The hypoxia inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia, however, little evidence was available from CKD models. Here, we assessed whether the pharmacological activation of HIF by MK-8617 (MK), a novel orally active HIF-PHI, improves CKD-associated myopathy. Mice were divided into Sham or CKD groups, and CKD mice were subdivided into CKD + vehicle or MK-treatment groups (1.5, 5 or 12.5 mg/kg for 12 weeks). In CKD mice, skeletal muscle mass, mitochondrial amount and exercise capacity decreased compared to Sham mice. Compared to the CKD + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) dose, but not high, significantly restored these changes and was accompanied by incremental increases in HIF-1α. Furthermore, increased capillary d...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research