AGE INFLUENCES THE REPLICATIVE ACTIVITY AND THE DIFFERENTIATION FEATURES OF CULTURED RAT AORTIC SMOOTH-MUSCLE CELL-POPULATIONS AND CLONES

The replicative activity and the differentiation features of aortic sm ooth muscle cells (SMCs) cultured as whole populations or clones from newborn (4-day-old), young adult (6-week-old), and old (18-month-old) rats were studied by means of cell counting, [H-3]thymidine incorporat ion, and measurement of the expression of cytoskeletal proteins and mR NAs. In whole populations at the fifth passage, replicative activity i ncreased and differentiation features (ie, expression of alpha-smooth muscle actin, desmin, and smooth muscle myosin heavy chains) decreased with increasing age of the donor animal. SMC clones derived from newb orn or young adult rats showed more differentiated cytoskeletal featur es than their parental populations; however, most SMC clones from old rats showed dedifferentiated features similar to those observed in the ir parental populations. Our results suggest that (1) SMCs of the rat aortic media behave as a heterogeneous population; (2) cultured whole SMC populations behave differently from clones as far as their replica tive activity and differentiation features are concerned; and (3) SMCs derived from old rats, whether grown as whole populations or as clone s, dedifferentiate more substantially and replicate more actively than corresponding cultures from newborn or young adult rats when submitte d to the same amount of serum growth factors; these differences may pl ay a role in arterial development as well as in the formation and evol ution of the atheromatous plaque.