High altitude long‐term hypoxia: Gene expression in adult ovine carotid arteries

Abstract

In humans and other species, exposure to long‐term high altitude (>;2500 m) is known to result in dysregulation of cerebral blood flow (CBF) as a consequence of low O2 tension. To elucidate the signal transduction pathways involved in successful acclimatization of sheep to high altitude, we tested the hypothesis that high‐altitude associated long‐term hypoxia (LTH) results in changes in gene expression of critical signaling pathways in ovine carotid arteries. To test this, we acclimatized non‐pregnant adult sheep to 3801 m altitude for about 100 days and conducted oligonucleotide microarray experiments on carotid arteries. A total of 60 and 58 genes were significantly (>; 2‐fold; P < 0.05) upregulated and downregulated, respectively. Major genes upregulated included suprabasin, myelin basic protein, apoliprotein B; whereas major downregulated genes included protein kinase C delta, endonucleas V, BCL6. Several of these genes belonged to ubiquonone canonical pathway. A number of upregulated genes had STAT3 and USP transcription factor binding sites. Similarly, a number of downregulated genes had a common binding sites for TOD6/DOT6 and ZBTB3 transcription repressor sites. In conclusion, the present study demonstrates novel signal transduction molecules involved in LTH acclimatization of sheep carotid arteries. The study was supported by PHS PO1 HD031226 to LDL.