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Molecular and Cellular Biochemistry 176: 53–59, 1997.
© 1997 Kluwer Academic Publishers. Printed in the Netherlands.
Introduction
The normal arterial vessel wall consists of a regular arrange-
ment of endothelial, smooth muscle and fibroblast cells,
present in three distinct layers of endothelium, media and
adventitia. A single layer of endothelial cells forms the
luminal barrier to blood-borne signals that modulate vascu-
lar function. The adventitia, which forms the outer layer
around the artery, consists primarily of extracellular matrix
as well as some fibroblasts, nerve fibres and microvessels.
The media consists of numerous layers of smooth muscle
cells (SMCs) intermixed with extracellular matrix that is
bound by the internal and external elastic lamina. In some
species such as swine and humans, an intima forms with
maturity that consists of SMCs located on the luminal side
of the internal elastic lamina.
The response to injury or other stress stimuli (e.g. stretch)
varies between the different cellular components of the
vessel. Endothelial cells are capable of proliferation and
migration, properties that permit re-endothelialization of the
vessel after denudation or injury [1]. Medial SMCs are also
able to reversibly modulate their phenotype which allows for
their proliferation and/or migration into the intima at the site
of injury [2]. It is these characteristics that lead to the adap-
tive and pathogenic growth of SMCs which is key to vascu-
lar remodelling and lesion formation. An emerging concept
is that the medial SMC population consists of heterogeneous
subpopulations of SMCs that differ in their growth and/or
Address for offprints: P. Zahradka, Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, Winnipeg, MB,
R2H 2A6, Canada
Coronary artery smooth muscle in culture:
Migration of heterogeneous cell populations from
vessel wall
Laura Saward and Peter Zahradka
Department of Physiology, University of Manitoba; Institute of Cardiovascular Sciences, St. Boniface General
Hospital Research Centre, Winnipeg, Manitoba, R2H 2A6, Canada
Abstract
A method for establishing primary cultures of smooth muscle cells (SMCs) from the porcine coronary artery without either
microdissection and/or enzymatic dispersion was developed using selective migration of cells from coronary explants in vitro.
This culture method relies on the heterogeneity of cell types and differences in their migration and adherence ability to sepa-
rate SMC from contaminating fibroblasts or endothelial cells. The cell type was determined by immunohistochemical staining
with monoclonal antibodies to SM α-actin, SM myosin, h-caldesmon and von Willebrand factor. The first wave of migration
(1–7 days) consisted of a mixture of fibroblasts and SMCs. Only SMCs were present in the second wave of migration (7–14
days). Endothelial cells, which exhibited a lower capacity for migration and adherence, were restricted to the third wave of
migration (14–21 days). Cells obtained from the second wave of migration exhibited the characteristic single-layered, aligned,
hill-and-valley pattern of SMCs when confluent. Quiescence was attained 4–5 days after removal of serum, as established by
[
3
H]-thymidine incorporation. Stimulation of the quiescent SMCs with 20% FBS resulted in a synchronous re-entry into the
cell-cycle with S phase reached 15–18 h later. The SMCs prepared using this protocol thus exhibit the structural markers and
capacity to undergo phenotypic modulation that are characteristic of SMCs in vivo. This approach to establishing primary cultures
of SMCs offers the advantage of selecting for the subpopulation of cells capable of migration in response to injury or growth
factor stimulation. (Mol Cell Biochem 176: 53–59, 1997)
Key words: smooth muscle, coronary artery, porcine, immunofluorescent microscopy