Evidence from a novel human cell clone that adult vascular smooth muscle cells can convert reversibly between noncontractile and contractile phenotypes

Smooth muscle cells (SMCs) perform diverse functions that can be categorize d as contractile and synthetic. A traditional model holds that these distin ct functions are performed by the same cell, by virtue of its capacity for bidirectional modulation of phenotype. However, this model has been challen ged, in part because there is no physiological evidence that an adult synth etic SMC can acquire the ability to contract. We sought evidence for this b y cloning adult SMCs from human internal thoracic artery. One clone, HITB5, expressed smooth muscle alpha-actin, smooth myosin heavy chains, heavy cal desmon, and calponin and showed robust calcium transients in response to hi stamine 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 p roduction fell, and cell proliferation and [H-3]thymidine incorporation fel l to near 0. Cell viability was not compromised, however; in fact, apoptosi s rate fell significantly. In this state, agonist-induced elevation of cyto plasmic calcium was even more: pronounced and was accompanied by SMC contra ction. Readdition of 10% serum completely-returned HITB5 cells to a noncont ractile, proliferative phenotype. contractile protein expression increased after serum withdrawal, although modestly, which suggested that the switch to contractile function involved reorganization or sensitization of existin g contractile structures. To our knowledge, the physiological properties of HITB5 SMCs provide the first direct demonstration that cultured human adul t SMCs can convert between a synthetic, noncontracting state and a contract ing state. HITB5 cells should be valuable for characterizing the basis of t his critical transition.