Phenotypic stability and variation in cells of the porcine aorta: collagen and XXXX production.

@entity1707 @entity13402 @entity2591 @entity3960
The extracellular matrix of the developing vasculature varies in composition as a function of time and position. Cellular models of vascular biology and pathology depend on the assumption that stable phenotypic characteristics of vascular cells can be propagated through several generations of in vitro cultivation. We show that the positional and developmental heterogeneity of matrix phenotypes in the porcine aorta are expressed by explanted vascular @entity3960 ( @entity3960 ) and adventitial cell populations for a limited number of passages. @entity13402 was expressed most highly by thoracic @entity3960 while interstitial collagen production was usually maximal in abdominal segments. Parallel gradients of collagen types I, III and V, detected by specific ELISA assays, were expressed in early-passage @entity3960 . Adventitial cell populations from the abdominal aorta of the neonatal @entity1707 accumulated significant levels of collagen, while these fibroblasts produced less than 10% of the @entity13402 made by @entity3960 . All cell populations expressed alpha-smooth muscle actin in vitro. Gradients of collagen and @entity13402 expression were evident for no more than three passages, and direct outgrowth of cells without limited digestion of the matrix further reduced phenotypic stability. Variation and decline of the @entity13402 phenotype could be due to hypermethylation of regulatory sequences in the @entity13402 gene or trans-acting factors, but @entity13402 production was dose-dependently stimulated to a similar extent (100%; 10 microM @entity2591 ) in all segmental @entity3960 populations at early (p1) and late (p3) passage. These data indicated that faithful reflection of in vivo @entity3960 behavior was limited to a few population doublings, at least under standard culture conditions. Modification of the cellular environment by reducing serum factors, changing matrix, or adding mechanical stimulation may increase phenotypic stability.
