Gene expression changes in the corpus cavernosum of hypercholesterolemic rats were not fully assessed, which were not previously known to be associated with
hypercholesterolemia-related
erectile dysfunction (ED). To provide molecular insight into pathophysiology of
hypercholesterolemia-related ED and to investigate the effects of
Udenafil, a
phosphodiesterase type 5 (
PDE5) inhibitor, on gene expression, we performed microarray gene expression analysis via gene discovery methods using GenoCheck
platinum cDNA chip (Ansan, S. Korea). Sixteen male Sprague-Dawley rats were fed 2%
cholesterol diet for 5 months. Half of them were orally treated with
Udenafil (20 mg/kg/day) simultaneously. Eight age-matched rats fed normal diet were served as normal control.
RNA was extracted from corpus cavernosum and microarray analysis was performed. Decreased erectile responses and
hypercholesterolemia were observed in hypercholesterolemic control group. In microarray analysis, 122 candidate genes were noted to be altered based on the magnitude of expression changes, which includes 44 down-regulated and 78 up-regulated genes compared with the age-matched normal controls. These changes were, however, significantly attenuated by treatment with
Udenafil. Out of the 78 up-regulated genes, 8 genes were significantly decreased by the chronic treatment with
Udenafil. The altered genes were
cytochrome oxidase biogenesis
protein OXA1, skeletal muscle
myosin heavy chain, lipophilin, fast skeletal muscle
isoforms beta/
alpha, myosin light chain 3,
cytochrome c oxidase, adipocyte
fatty acid binding protein and one EST gene. In contrast, among the 44 down-regulated genes,
Kruppel-like factor 5 and cyclin D1 genes were increased after the
Udenafil treatment. These results provide the molecular basis for understanding the pathogenesis of
hypercholesterolemia-related ED and offer clues on determining the underlying action mechanism of a
PDE5 inhibitor.