Published online before print August 30, 2001, doi: 10.1161/hh1801.097165
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Cellular Biology |
Innate Diversity of Adult Human Arterial Smooth Muscle Cells
Cloning of Distinct Subtypes From the Internal Thoracic Artery
From the John P. Robarts Research Institute (Vascular Biology Group) (S.L., L.H.C., C.V.D.D., E.V.D.V., J.G.P.), London Health Science Centre (Y.F., L.H.C., J.G.P.), Departments of Pathology (Y.F.), Medicine (Cardiology) (L.H.C., J.G.P.), Physiology (S.M.S.), Biochemistry (J.G.P.), and Medical Biophysics (J.G.P.), University of Western Ontario, London, Canada.
Correspondence to J. Geoffrey Pickering, MD, PhD, London Health Science Centre, 339 Windermere Rd, London, Ontario N6A 5A5. E-mail gpickering{at}rri.on.ca
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) 
-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 -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.
Key Words: vascular smooth muscle • proliferation • migration • gene expression
This article has been cited by other articles:
 |
|
 |
|
  E. van der Veer, C. Ho, C. O'Neil, N. Barbosa, R. Scott, S. P. Cregan, and J. G. Pickering Extension of Human Cell Lifespan by Nicotinamide Phosphoribosyltransferase J. Biol. Chem., April 13, 2007; 282(15): 10841 - 10845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gros, Q. Ding, S. Armstrong, C. O'Neil, J. G. Pickering, and R. D. Feldman Rapid effects of aldosterone on clonal human vascular smooth muscle cells Am J Physiol Cell Physiol, February 1, 2007; 292(2): C788 - C794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. W. Small, Z. Bolender, C. Bueno, C. O'Neil, Z. Nong, W. Rushlow, N. Rajakumar, C. Kandel, J. Strong, J. Madrenas, et al. Wilms' Tumor 1-Associating Protein Regulates the Proliferation of Vascular Smooth Muscle Cells Circ. Res., December 8, 2006; 99(12): 1338 - 1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G.M. Molin and M. J. Post Do intrinsic arterial wall features determine atherosclerosis susceptibility? Cardiovasc Res, October 1, 2006; 72(1): 3 - 4. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sainz and M. Sata Maintenance of Vascular Homeostasis by Bone Marrow-Derived Cells. Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1196 - 1197. [Full Text] [PDF]
|
|
|
|
|
|
M. Sata Role of Circulating Vascular Progenitors in Angiogenesis, Vascular Healing, and Pulmonary Hypertension: Lessons From Animal Models Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1008 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yaghi and S. M. Sims Constrictor-induced translocation of NFAT3 in human and rat pulmonary artery smooth muscle Am J Physiol Lung Cell Mol Physiol, December 1, 2005; 289(6): L1061 - L1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. W. Q. Moore and D. Y. Hui Apolipoprotein E inhibition of vascular hyperplasia and neointima formation requires inducible nitric oxide synthase J. Lipid Res., October 1, 2005; 46(10): 2083 - 2090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. van der Veer, Z. Nong, C. O'Neil, B. Urquhart, D. Freeman, and J. G. Pickering Pre-B-Cell Colony-Enhancing Factor Regulates NAD+-Dependent Protein Deacetylase Activity and Promotes Vascular Smooth Muscle Cell Maturation Circ. Res., July 8, 2005; 97(1): 25 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Greaves and S. Gordon Thematic review series: The Immune System and Atherogenesis. Recent insights into the biology of macrophage scavenger receptors J. Lipid Res., January 1, 2005; 46(1): 11 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, P. J. Rao, M. R. Castresana, and W. H. Newman TNF-{alpha} induces proliferation or apoptosis in human saphenous vein smooth muscle cells depending on phenotype Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H293 - H301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sata and R. Nagai Origin of Neointimal Cells in Autologous Vein Graft Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1147 - 1149. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Argmann, C. G. Sawyez, S. Li, Z. Nong, R. A. Hegele, J. G. Pickering, and M. W. Huff Human Smooth Muscle Cell Subpopulations Differentially Accumulate Cholesteryl Ester When Exposed to Native and Oxidized Lipoproteins Arterioscler. Thromb. Vasc. Biol., July 1, 2004; 24(7): 1290 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Andres Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential Cardiovasc Res, July 1, 2004; 63(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gui and X.-L. Zheng Epidermal Growth Factor Induction of Phenotype-dependent Cell Cycle Arrest in Vascular Smooth Muscle Cells Is through the Mitogen-activated Protein Kinase Pathway J. Biol. Chem., December 26, 2003; 278(52): 53017 - 53025. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tintut, Z. Alfonso, T. Saini, K. Radcliff, K. Watson, K. Bostrom, and L. L. Demer Multilineage Potential of Cells From the Artery Wall Circulation, November 18, 2003; 108(20): 2505 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tanaka, M. Sata, Y. Hirata, and R. Nagai Diverse Contribution of Bone Marrow Cells to Neointimal Hyperplasia After Mechanical Vascular Injuries Circ. Res., October 17, 2003; 93(8): 783 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Stiebellehner, M. G. Frid, J. T. Reeves, R. B. Low, M. Gnanasekharan, and K. R. Stenmark Bovine distal pulmonary arterial media is composed of a uniform population of well-differentiated smooth muscle cells with low proliferative capabilities Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L819 - L828. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hao, G. Gabbiani, and M.-L. Bochaton-Piallat Arterial Smooth Muscle Cell Heterogeneity: Implications for Atherosclerosis and Restenosis Development Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1510 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Van Den Diepstraten, K. Papay, Z. Bolender, A. Brown, and J. G. Pickering Cloning of a Novel Prolyl 4-Hydroxylase Subunit Expressed in the Fibrous Cap of Human Atherosclerotic Plaque Circulation, August 5, 2003; 108(5): 508 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Karkanis, S. Li, J. G. Pickering, and S. M. Sims Plasticity of KIR channels in human smooth muscle cells from internal thoracic artery Am J Physiol Heart Circ Physiol, June 1, 2003; 284(6): H2325 - H2334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sata, K. Tanaka, R. Nagai, Y. Hu, H. Dietrich, F. Davison, M. Mayr, Q. Xu, B. Ludewig, M. Erdel, et al. Origin of Smooth Muscle Progenitor Cells: Different Conclusions From Different Models * Response Circulation, April 29, 2003; 107 (16): e106 - e107. [Full Text] [PDF]
|
|
|
|
|
|
M. H. Laughlin, J. R. Turk, W. G. Schrage, C. R. Woodman, and E. M. Price Influence of coronary artery diameter on eNOS protein content Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1307 - H1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gabbiani and G. K. Hansson ATVB In Focus: Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., March 1, 2003; 23(3): 379 - 379. [Full Text] [PDF]
|
|
|
|
|
|
C. Castro, A. Diez-Juan, M. J. Cortes, and V. Andres Distinct Regulation of Mitogen-activated Protein Kinases and p27Kip1 in Smooth Muscle Cells from Different Vascular Beds. A POTENTIAL ROLE IN ESTABLISHING REGIONAL PHENOTYPIC VARIANCE J. Biol. Chem., February 7, 2003; 278(7): 4482 - 4490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Woo and T. J. Gardner Myocardial Revascularization with Cardiopulmonary Bypass Card. Surg. Adult, January 1, 2003; 2(2003): 581 - 607. [Full Text]
|
|
|
|
|
|
E. F. Rocnik, E. van der Veer, H. Cao, R. A. Hegele, and J. G. Pickering Functional Linkage between the Endoplasmic Reticulum Protein Hsp47 and Procollagen Expression in Human Vascular Smooth Muscle Cells J. Biol. Chem., October 4, 2002; 277(41): 38571 - 38578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.S.M Rensen, V.L.J.L Thijssen, C.J De Vries, P.A Doevendans, S.D Detera-Wadleigh, and G.J.J.M Van Eys Expression of the smoothelin gene is mediated by alternative promoters Cardiovasc Res, September 1, 2002; 55(4): 850 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hao, P. Ropraz, V. Verin, E. Camenzind, A. Geinoz, M. S. Pepper, G. Gabbiani, and M.-L. Bochaton-Piallat Heterogeneity of Smooth Muscle Cell Populations Cultured From Pig Coronary Artery Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1093 - 1099. [Abstract] [Full Text] [PDF]
|
|