Gene expression profiling of an arteriogenic impotence model.
Penile arterial insufficiency is one of the most common causes of ED. We have established a traumatic arteriogenic insufficiency rat model by the ligation of the pudendal arteries. To simulate both acute and chronic traumatic injuries, five ligation periods (6 h, 3 days, 7 days, 3 weeks, and 6 weeks) were chosen. By electrostimulation of the cavernous nerve, the intracavernous pressure was determined to be between 20 and 40-cm H(2)O for the ligated rats compared to around 100-cm H(2)O for the control rats. The erectile tissue in the corpus cavernosum of these rats was then subjected to microarray analysis, in which an array that contains cDNA fragments representing 1176 rat genes was used. The results demonstrated that normal rat corpus cavernosum expressed approximately 200 genes at detectable levels and that ligation produced differential expression of approximately 25 genes, depending on the duration of ligation. The most highly ligation-induced gene was apolipoprotein D (ApoD), with peak expression in the 3- and 7-day ligated rats. Three of the insulin-like growth factor binding proteins (IGFBP-1, 3, and 5) were upregulated in all ligated rats. IGFBP-6, which was one of the most highly expressed genes in the normal corpus cavernosum, was down-regulated in all ligated rats. Cysteine proteases of the cathepsin family were also differentially expressed between control and ligated rats, with cathepsin K being down-regulated most. A few genes were upregulated only in the 6-week ligated rats, including angiotensin-converting enzyme. Finally, VEGF, whose induction has been identified in many other ischemic tissues, was not induced in corpus cavernous tissue of ligated rats.
Lin
C S
CS
Knuppe Molecular Urology Laboratory, School of Medicine, University of California at San Francisco, San Francisco, CA 94143-1695, USA. clin@urol.ucsf.edu
Ho
H C
HC
Gholami
S
S
Chen
K C
KC
Jad
A
A
Lue
T F
TF
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D053399:Apolipoproteins D; D004195:Disease Models, Animal; D004558:Electric Stimulation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D018783:Impotence, Vasculogenic / Q000235:genetics*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics; D008297:Male; D010413:Penis / Q000294:innervation; D011506:Proteins / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001053:Apolipoproteins; D053399:Apolipoproteins D; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D011506:Proteins