Abstract
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 μm in length, and had a doubling time of 39±2 hours. Spindle-shaped clones (n=3) were larger (267±18 μm long, P<0.01) and grew slower (doubling time 65±4 hours, P<0.01). Both types of clones expressed smooth muscle (SM) α-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 Ca2+ 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 α-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.
| Original language | English |
|---|---|
| Pages (from-to) | 517-525 |
| Number of pages | 9 |
| Journal | Circulation Research |
| Volume | 89 |
| Issue number | 6 |
| State | Published - Sep 14 2001 |
| Externally published | Yes |
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Keywords
- Gene expression
- Migration
- Proliferation
- Vascular smooth muscle
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Innate diversity of adult human arterial smooth muscle cells : Cloning of distinct subtypes from the internal thoracic artery. / Li, Shaohua; Fan, Yao-Shan; Chow, Lawrence H.; Van Den Diepstraten, Caroline; Van der Veer, Eric; Sims, Stephen M.; Pickering, J. Geoffrey.
In: Circulation Research, Vol. 89, No. 6, 14.09.2001, p. 517-525.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Innate diversity of adult human arterial smooth muscle cells
T2 - Cloning of distinct subtypes from the internal thoracic artery
AU - Li, Shaohua
AU - Fan, Yao-Shan
AU - Chow, Lawrence H.
AU - Van Den Diepstraten, Caroline
AU - Van der Veer, Eric
AU - Sims, Stephen M.
AU - Pickering, J. Geoffrey
PY - 2001/9/14
Y1 - 2001/9/14
N2 - 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 μm in length, and had a doubling time of 39±2 hours. Spindle-shaped clones (n=3) were larger (267±18 μm long, P<0.01) and grew slower (doubling time 65±4 hours, P<0.01). Both types of clones expressed smooth muscle (SM) α-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 Ca2+ 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 α-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.
AB - 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 μm in length, and had a doubling time of 39±2 hours. Spindle-shaped clones (n=3) were larger (267±18 μm long, P<0.01) and grew slower (doubling time 65±4 hours, P<0.01). Both types of clones expressed smooth muscle (SM) α-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 Ca2+ 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 α-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.
KW - Gene expression
KW - Migration
KW - Proliferation
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0035860837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035860837&partnerID=8YFLogxK
M3 - Article
VL - 89
SP - 517
EP - 525
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 6
ER -