VEGF189Expression Is Highly Related to Adaptation of the Plateau Pika (Ochotona curzoniae) Inhabiting High Altitudes

Li, Hongge, Songchang Guo, Yongming Ren, Depeng Wang, Honghao Yu, Wenjing Li, Xinquan Zhao, and Zhijie Chang. VEGF(189) expression is highly related to adaptation of the plateau pika (Ochotona curzoniae) inhabiting high altitudes. High Alt Med Biol 14:395-404, 2013. The plateau pika (Ochotona curzonia) has adapted to high-altitude hypoxia during evolution. Higher microvessel density in specific tissues and a blunted hypoxic pulmonary vasoconstriction response are the critical components of this adaptation. VEGF, vascular endothelial growth factor, has proved to be a key regulator of angiogenesis in response to tissue hypoxia and to play an important role in vascular vasodilation. However, the role of VEGF in adaptation to high-altitude hypoxia in the plateau pika remains unknown. In this study, we cloned cDNAs for VEGF(165) and VEGF(189) and examined their expression in pikas inhabiting altitudes of 3200 and 4750m. Phylogenetic analysis reveals that pika VEGF(165) and VEGF(189) are evolutionarily conserved. Real-time PCR analysis demonstrates that VEGF(165) and VEGF(189) display tissue and altitude-specific expression patterns. Interestingly, we found that the levels of VEGF(189) mRNA are significantly higher than those of VEGF(165) in the brain and muscle tissues of the pika, which is different from what was previously observed in sea-level mammals. VEGF(189) mRNA levels in brain, muscle, and lung of the pika increased with increased habitat altitude, whereas VEGF(165) shows less change. Our study suggests an important role for VEGF(189) in adaptation to hypoxia by the plateau pika in the high-altitude environment.