Differential gene expression in primary and recurrent carotid stenosis.

Apoptosis of the cellular components of complex atherosclerotic plaque may lead to plaque instability and rupture. In this study, five primary plaques and one recurrent fibrointimal lesion obtained from patients undergoing carotid endarterectomy for symptomatic carotid stenosis > or = 70% were analyzed by immunohistochemistry and cDNA microarray to identify gene expression patterns that may determine plaque susceptibility or resistance to apoptosis. Immunohistochemistry showed expression of active caspase 3, an effector of apoptosis, in macrophages and lymphocytes surrounding the lipid core, in smooth muscle cells in the fibrous cap, and media of primary plaques as well as in occasional smooth muscle cells in the recurrent lesion. Among the genes demonstrating increased expression in primary plaques were IGFR2, DR4, DAPK1, Bak, and ERK 1 and 2 and those showing decreased expression included the TNF receptors 1 and 2, akt1, and IGFBP3. When comparing the recurrent lesion to the normal tissue, the expression of 13 genes was decreased by 3-fold, including IGFBP2 and IGFBP3, and none were increased by more than 1.5-fold. The analysis of gene expression patterns in primary and recurrent stenotic lesions provides a powerful approach to identify the signaling pathways that alter cellular apoptotic patterns in such lesions.

Effect of aging on the adaptive and proliferative capacity of the small bowel.

Our society is aging at a rapid rate; the effects of aging on physiologic functions (e.g., small bowel adaptation) are poorly understood. The purpose of this study was to determine the ability of the aged small bowel mucosa to adapt after resection. Young (2-month-old) and aged (24-month-old) F344 rats underwent massive (70%) proximal small bowel resection (SBR) or sham operation; rats were killed at 9 or 16 days after surgery. The remnant small bowel and corresponding sham segments were harvested, weighed, and analyzed for DNA content and villus height. To determine whether the adaptive response after SBR could be enhanced, aged rats underwent SBR or sham operation and were treated with either neurotensin or saline solution (control). SBR resulted in adaptive hyperplasia in the remaining small bowel remnant in both young and aged rats at 9 and 16 days compared with sham animals. At 9 days, significant increases were noted in weight, villus height, and DNA content of the distal remnant in young and aged rats after SBR; the increases were similar in both young and aged rats. At 16 days, both young and aged rats displayed significant increases in remnant weight after SBR. Administration of neurotensin increased the weight of the remnant intestine in aged rats after SBR compared with saline treatment. Our findings demonstrate that aged small bowel mucosa exhibits a proliferative and adaptive capacity in response to SBR that was similar to that of the young animals. In addition, neurotensin administration enhanced the normal adaptive response of the small bowel in aged rats, providing further evidence that neurotensin may be therapeutically useful to augment mucosal regeneration in the early periods after massive SBR.