We have previously shown that simvastatin attenuates chronic hypoxic pulmonary hypertension. To explore the potential mechanisms, microarray analysis was performed on whole lungs from Sprague-Dawley rats (Hilltop; Scottsdale, PA) that had been exposed to normoxia, chronic hypoxia (ie, 10% fraction of inspired oxgyen for 14 days) or hypoxia plus simvastatin, 20 mg/kg/d intraperitoneally. RNA (n = 3 in each group, analyzed separately) was hybridized to the genome array (Rat Genome U34A array; Affymetrix; Santa Clara, CA). Comparisons of mice exposed to chronic hypoxia vs those exposed to normoxia, and mice exposed to hypoxia plus simvastatin vs those exposed to chronic hypoxia were performed with significance analysis of microarrays to identify genes with a change of more than twofold and a false discovery rate of < 10%. One hundred ten genes were positively expressed in mice exposed to chronic hypoxia vs those exposed to normoxia, while 20 genes were down-regulated. Increased expression of 9 genes and a reduction in 143 genes was observed for mice exposed to hypoxia plus simvastatin vs those exposed to chronic hypoxia. Table 1
shows a list of candidate genes that were differentially expressed in both comparisons.