Innate diversity of adult human arterial smooth muscle cells - Cloning of distinct subtypes from the internal thoracic artery

Vascular smooth muscle cells (SMCs) perform diverse functions and this func tional heterogeneity could be based on differential recruitment of distinct SMC subsets. In humans, however, there is little support for such a paradi gm, partly because isolation of pure human SMC subsets has proven difficult . We report the cloning of 12 SMC lines from a single fragment of human int ernal thoracic artery and the elucidation of 2 distinct cellular profiles. Epithelioid clones (n=9) were polygonal at confluence, 105 +/-9 mum in leng th, and had a doubling time of 39 +/-2 hours. Spindle-shaped clones (n=3) w ere larger (267 +/- 18 Am long, P < 0.01) and grew slower (doubling time 65 +/-4 hours, P < 0.01). Both types of clones expressed smooth muscle (SM) a lpha -action, SM-myosin heavy chains, h-caldesmon, and calponin, but only s pindle-shaped clones expressed metavinculin. Epithelioid clones displayed g reater proliferation in response to platelet-derived growth factor-BB and f ibroblast growth factor-2 and were more responsive to the migratory effect of platelet-derived growth factor-BB. Spindle-shaped clones showed more rob ust Ca2+ transients in response to angiotensin II, histamine, and norepinep hrine, crawled more quickly, and expressed more type I collagen. On serum w ithdrawal, spindle-shaped clones differentiated into a contraction-competen t cell. A regional basis for diversity among SMCs was suggested by stepwise arterial digestion, which liberated small, SM a-actin-positive cells from the abluminal medial layers and larger SMCs from all layers. These results identify inherent SMC diversity in the media of the adult internal thoracic artery and suggest differential participation of SMC subsets in the regula tion of human arterial behavior.