Induction of angiotensin converting enzyme in neointima after intravascular stent placement.

BACKGROUND: To investigate the morphological changes of the arterial wall and the expression of angiotensin converting enzyme (ACE) in the arterial wall after stent placement in a canine model. METHODS: Seventeen mongrel dogs underwent stent placement (Gianturco's Z stent) in the aorta. Six animals were sacrificed at 4 weeks after stent implantation, and the other 5 animals at 12 weeks. The normal aorta was harvested from 6 dogs. The specimens were stained with hematoxylin-eosin (H&E) as well as by immunohistochemistry (smooth muscle specific a-actin, and ACE). Histomorphometric analysis was performed using the sections stained with H&E and smooth muscle specific a-actin. RESULTS: The total intimal area was significantly increased at all time points as compared with the control aorta. The a-actin positive intimal area was also significantly increased at all time points as compared with the control aorta. In the control aorta, luminal endothelial cells as well as a-actin positive medial cells occasionally exhibited faint cytoplasmic staining for ACE. In the 4- and 12-week stented aorta, a-actin positive cells in the neointima and media as well as macrophages in the adventitia stained strongly positive for ACE. CONCLUSIONS: ACE was induced in the neointima after stent placement of the canine aorta. Considering its multiple biological actions, ACE may be associated with the pathogenesis of neointimal hyperplasia after stent placement.

Drastic genetic instability of tumors and normal tissues in Turcot syndrome.

Turcot syndrome is characterized by an association of malignant brain tumors and colon cancer developing in the patient's teens. Since the mechanism of carcinogenesis in Turcot syndrome is still unclear, we analysed genetic changes in tumors from a Turcot patient with no family history of the condition. All tumors, including one astrocytoma, three colon carcinomas, and two colon adenomas, exhibited severe replication error (RER), and all colon tumors showed somatic mutations at repeated regions of TGFbetaRII, E2F-4, hMSH3, and/or hMSH6 genes. Somatic APC mutations were detected in three of three colon carcinomas, and somatic p53 mutations were detected in the astrocytoma and two of three colon carcinomas, both of which showed two mutations without allele loss. We also found that normal colon mucosa, normal skin fibroblasts and normal brain tissue from this patient showed respective high frequencies of RER, in contrast to usual HNPCC patients in which RER was very rare in normal tissues. These results suggest that extreme DNA instability in normal tissues causes the early development of multiple cancer in Turcot syndrome. A missense mutation (GAG to AAG) at codon 705 of hPMS2 gene was detected in one allele of this patient, which was inherited from his mother without tumors. Additional unknown germline mutation may contribute to the genetic instability in normal tissues.