Gene expression profiling of an arteriogenic impotence model

Penile arterial insufficiency is one of the most common causes of ED. We ha ve established a traumatic arteriogenic insufficiency rat model by the liga tion 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 intracaver nous pressure was determined to be between 20 and 40-cm H2O for the ligated rats compared to around 100-cm H2O for the control rats. The erectile tiss ue 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 caverno sum expressed approximately 200 genes at detectable levels and that ligatio n produced differential expression of approximately 25 genes, depending on the duration of ligation. The most highly ligation induced gene was apolipo protein D (ApoD), with peak expression in the 3- and 7-day ligated rats. Th ree 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 hi ghly expressed genes in the normal corpus cavernosum, was down-regulated in all ligated rats. Cysteine proteases of the cathepsin family were also dif ferentially expressed between control and ligated rats, with cathepsin K be ing down-regulated most. A few genes were upregulated only in the 6-week li gated rats, including angiotensin-converting enzyme. Finally, VEGF, whose induction has been identified in many other ischemic tissues, was not induc ed in corpus cavernous tissue of Ligated rats. (C) 2001 Academic Press.