SOLUBLE FACTORS MODULATE CHANGES IN COLLAGEN GENE-EXPRESSION IN ABDOMINAL AORTIC-ANEURYSMS

Background. Although increased procollagen gene expression and synthes is have been implicated in the progression of abdominal aortic aneurys ms (AAA), factors modulating this change have not been identified. Fur thermore, it is not known whether the increase in AAA procollagen expr ession is specific to this disease or also occurs in tissue affected b y atherosclerotic occlusive disease (AOD). If paracrine rather than au tocrine factors are responsible for increased gene expression in AAA, this effect should be transferable to target smooth muscle cells throu gh conditioned media. Our objectives were to determine 1alpha (I) proc ollagen messenger RNA levels in AOD tissue compared with normal and AA A and to determine whether differences noted in tissue procollagen gen e expression could be transferred through conditioned media from norma l, AOD, and AAA tissues to target smooth muscle cells in primary cultu re. Methods. Normal, AOD, and AAA tissue was used for tissue RNA extra ction or was minced and washed with serum-free media (4-degrees-C) X 3 0 minutes and the media applied to human aortic smooth muscle cells (S MC) in primary culture for 36 hours. Total RNA from tissue and SMC exp osed to conditioned media was analyzed by Northern and dot blot analys is for 1alpha (I) procollagen. Results. Relative tissue 1alpha (I) pro collagen 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 1alpha (I) procollagen levels in SMC expos ed 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). Conclus ions. 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 paracri ne, rather than autocrine, factors modulate procollagen expression in AAA tissues.