Innate diversity of adult human arterial smooth muscle cells

Cloning of distinct subtypes from the internal thoracic artery

Shaohua Li, Yao-Shan Fan, Lawrence H. Chow, Caroline Van Den Diepstraten, Eric Van der Veer, Stephen M. Sims, J. Geoffrey Pickering

Research output: Contribution to journalArticle

118 Citations (Scopus)

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 languageEnglish
Pages (from-to)517-525
Number of pages9
JournalCirculation Research
Volume89
Issue number6
StatePublished - Sep 14 2001
Externally publishedYes

Fingerprint

Mammary Arteries
Smooth Muscle Myocytes
Organism Cloning
Clone Cells
Smooth Muscle
Actins
Smooth Muscle Myosins
Calmodulin-Binding Proteins
Myosin Heavy Chains
Fibroblast Growth Factor 2
Collagen Type I
Vascular Smooth Muscle
Angiotensin II
Histamine
Digestion
Norepinephrine
Cell Line
Serum

Keywords

  • Gene expression
  • Migration
  • Proliferation
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Li, S., Fan, Y-S., Chow, L. H., Van Den Diepstraten, C., Van der Veer, E., Sims, S. M., & Pickering, J. G. (2001). Innate diversity of adult human arterial smooth muscle cells: Cloning of distinct subtypes from the internal thoracic artery. Circulation Research, 89(6), 517-525.

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 journalArticle

Li, S, Fan, Y-S, Chow, LH, Van Den Diepstraten, C, Van der Veer, E, Sims, SM & Pickering, JG 2001, 'Innate diversity of adult human arterial smooth muscle cells: Cloning of distinct subtypes from the internal thoracic artery', Circulation Research, vol. 89, no. 6, pp. 517-525.
Li, Shaohua ; Fan, Yao-Shan ; Chow, Lawrence H. ; Van Den Diepstraten, Caroline ; Van der Veer, Eric ; Sims, Stephen M. ; Pickering, J. Geoffrey. / Innate diversity of adult human arterial smooth muscle cells : Cloning of distinct subtypes from the internal thoracic artery. In: Circulation Research. 2001 ; Vol. 89, No. 6. pp. 517-525.
@article{bb6bfe73b60d40dcab740342e47c8dcc,
title = "Innate diversity of adult human arterial smooth muscle cells: Cloning of distinct subtypes from the internal thoracic artery",
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.",
keywords = "Gene expression, Migration, Proliferation, Vascular smooth muscle",
author = "Shaohua Li and Yao-Shan Fan and Chow, {Lawrence H.} and {Van Den Diepstraten}, Caroline and {Van der Veer}, Eric and Sims, {Stephen M.} and Pickering, {J. Geoffrey}",
year = "2001",
month = "9",
day = "14",
language = "English",
volume = "89",
pages = "517--525",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

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 -