Microarray analysis of gene expression profile in the corpus cavernosum of hypercholesterolemic rats after chronic treatment with PDE5 inhibitor.
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.
Jung
Han Gook
HG
Research Institutes of Dong-A Pharmaceutical Company, 47-5 Sanggal, Kiheung, Youngin, Kyunggi 449-905, Republic of Korea.
Shin
Jee Hyun
JH
Kim
Ko-Woon
KW
Yu
Jae Young
JY
Kang
Kyung Koo
KK
Ahn
Byoung Ok
BO
Kwon
Jong Won
JW
Yoo
Moohi
M
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D007172:Erectile Dysfunction / Q000235:genetics* / Q000503:physiopathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006937:Hypercholesterolemia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010413:Penis / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D002791:Cholesterol, Dietary; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides