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 functional heterogeneity could be based on differential recruitment of distinct SMC subsets. In humans, however, there is little support for such a paradigm, 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 internal thoracic artery and the elucidation of 2 distinct cellular profiles. Epithelioid clones (n=9) were polygonal at confluence, 105+/-9 micrometer in length, and had a doubling time of 39+/-2 hours. Spindle-shaped clones (n=3) were larger (267+/-18 micrometer long, P<0.01) and grew slower (doubling time 65+/-4 hours, P<0.01). Both types of clones expressed smooth muscle (SM) alpha-actin, SM-myosin heavy chains, h-caldesmon, and calponin, but only spindle-shaped clones expressed metavinculin. Epithelioid clones displayed greater proliferation in response to platelet-derived growth factor-BB and fibroblast growth factor-2 and were more responsive to the migratory effect of platelet-derived growth factor-BB. Spindle-shaped clones showed more robust Ca(2+) transients in response to angiotensin II, histamine, and norepinephrine, crawled more quickly, and expressed more type I collagen. On serum withdrawal, spindle-shaped clones differentiated into a contraction-competent cell. A regional basis for diversity among SMCs was suggested by stepwise arterial digestion, which liberated small, SM alpha-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 regulation of human arterial behavior.
Li
S
S
John P. Robarts Research Institute, London Health Science Centre, Department of Pathology, University of Western Ontario, London, Canada.
Fan
Y S
YS
Chow
L H
LH
Van Den Diepstraten
C
C
van Der Veer
E
E
Sims
S M
SM
Pickering
J G
JG
D000199:Actins / Q000378:metabolism; D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D000077214:Becaplermin; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003470:Culture Media / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D007621:Karyotyping; D008323:Mammary Arteries / Q000166:cytology*; D008840:Microfilament Proteins; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D013997:Time Factors; D000096985:Calponins
D000199:Actins; D000804:Angiotensin II; D000077214:Becaplermin; D002118:Calcium; D002135:Calcium-Binding Proteins; D002148:Calmodulin-Binding Proteins; D003470:Culture Media; D018076:DNA, Complementary; D016222:Fibroblast Growth Factor 2; D008840:Microfilament Proteins; D018995:Myosin Heavy Chains; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000096985:Calponins