SMOOTH-MUSCLE CELLS ISOLATED FROM DISCRETE COMPARTMENTS OF THE MATUREVASCULAR MEDIA EXHIBIT UNIQUE PHENOTYPES AND DISTINCT GROWTH CAPABILITIES

Heterogeneity of smooth muscle cell (SMC) phenotype and function is ra pidly emerging as an important concept. We have recently described tha t phenotypically distinct SMC subpopulations in bovine pulmonary arter ies exhibit unique proliferative and matrix-producing responses to hyp oxic pulmonary hypertension. To provide better understanding of the mo lecular mechanisms contributing to this phenomenon, experimental studi es will require a reliable in vitro model. The purpose of the present study was first to determine if distinct SMC subpopulations, similar t o those observed in vivo, could be selectively isolated from the matur e arterial media, and then to evaluate whether select SMC subpopulatio ns would exhibit heightened responses to growth-promoting stimuli and hypoxia. We were able to reproducibly isolate at least four phenotypic ally unique cell subpopulations from the inner, middle, and outer comp artments of the arterial media. Differences in cell phenotype were dem onstrated by morphological appearance and differential expression of m uscle-specific proteins. The isolated cell subpopulations exhibited ma rkedly different growth capabilities. Two SMC subpopulations grew slow ly in 10% serum and were quiescent in plasma-based medium. The other t wo cell subpopulations, exhibiting nonmuscle characteristics, grew rap idly in 10% serum and proliferated in plasma-based medium and in respo nse to hypoxia. Certain colonies of the nonmuscle-like cell subpopulat ions were found to grow autonomously under serum-deprived conditions a nd to secrete mitogenic factors. Our data, demonstrating that phenotyp ically distinct cells with enhanced growth potential exist within the normal arterial media, support the idea that these unique cells could contribute selectively to the pathogenesis of vascular disease.