Soluble factors modulate changes in collagen gene expression in abdominal aortic aneurysms

Background. Although increased procollagen gene expression and synthesis have been implicated in the progression of abdominal aortic aneurysms (AAA), factors modulating this change have not been identified. Furthermore, it is not known whether the increase in AAA procollagen expression is specific to this disease or also occurs in tissue affected by atherosclerotic occlusive disease (AOD). If paracrine rather than autocrine factors are responsible for increased gene expression in AAA, this effect should be transferable to target smooth muscle cells through conditioned media. Our objectives were to determine 1α(I) procollagen messenger RNA levels in AOD tissue compared with normal and AAA and to determine whether differences noted in tissue procollagen gene expression could be transferred through conditioned media from normal, AOD, and AAA tissues to target smooth muscle cells in primary culture. Methods. Normal, AOD, and AAA tissue was used for tissue RNA extraction or was minced and washed with serum-free media (4° C) X 30 minutes and the media applied to human aortic smooth muscle cells (SMC) in primary culture for 36 hours. Total RNA from tissue and SMC exposed to conditioned media was analyzed by Northern and dot blot analysis for 1α(I) procollagen. Results. Relative tissue 1α(I) procollagen levels were not increased in AOD (0.23 ± 0.05) as compared with normal (0.17 ± 0.03); both were decreased compared with AAA (0.53 ± 0.07; p < 0.01). The 1α(I) procollagen levels in SMC exposed to conditioned media from AAA (1.73 ± 0.15) were increased (p < 0.05) compared with AOD (1.10 ± 0.12) and normal (1.16 ± 0.16). Conclusions. There is no increase in tissue AOD procollagen gene expression. The ability to transfer the same relative patterns of gene expression from tissue to target SMC with conditioned media suggests that paracrine, rather than autocrine, factors modulate procollagen expression in AAA tissues.