© 1999 American Heart Association, Inc.
Cellular Biology |
Evidence From a Novel Human Cell Clone That Adult Vascular Smooth Muscle Cells Can Convert Reversibly Between Noncontractile and Contractile Phenotypes
From the Vascular Biology Group (S.L., L.H.C., J.G.P.), John P. Robarts Research Institute; Department of Medicine (Cardiology) (L.H.C., J.G.P.), London Health Sciences Centre; and Departments of Biochemistry (J.G.P.), Medical Biophysics (J.G.P.), and Physiology (S.S., Y.J.), University of Western Ontario, London, Ontario, Canada.
Correspondence to J. Geoffrey Pickering, MD, PhD, FRCP(C), London Health Sciences Centre, 339 Windermere Rd, London, Ontario N6A 5A5, Canada. E-mail gpickrng{at}rri.on.ca
Abstract—Smooth muscle cells
(SMCs) perform diverse functions that can be categorized as contractile
and synthetic. A traditional model holds that these distinct functions
are performed by the same cell, by virtue of its capacity for
bidirectional modulation of phenotype. However, this model has
been challenged, in part because there is no
physiological evidence that an adult synthetic SMC
can acquire the ability to contract. We sought evidence for this by
cloning adult SMCs from human internal thoracic artery. One clone,
HITB5, expressed smooth muscle 
-actin, smooth myosin heavy chains,
heavy caldesmon, and calponin and showed robust calcium transients in
response to histamine and angiotensin II, which confirmed
intact transmembrane signaling cascades. On serum withdrawal, these
cells adopted an elongated and spindle-shaped morphology, random
migration slowed, extracellular matrix protein production fell,
and cell proliferation and [3H]thymidine incorporation
fell to near 0. Cell viability was not compromised, however; in fact,
apoptosis rate fell significantly. In this state,
agonist-induced elevation of cytoplasmic calcium was even more
pronounced and was accompanied by SMC contraction. Readdition of 10%
serum completely returned HITB5 cells to a noncontractile,
proliferative phenotype. Contractile protein expression
increased after serum withdrawal, although modestly, which suggested
that the switch to contractile function involved reorganization or
sensitization of existing contractile structures. To our knowledge, the
physiological properties of HITB5 SMCs provide the
first direct demonstration that cultured human adult SMCs can convert
between a synthetic, noncontracting state and a contracting state.
HITB5 cells should be valuable for characterizing the basis of this
critical transition.
Key Words: muscle, smooth, vascular • differentiation • contraction • cell movement
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