Vascular repair and remodeling represents a common theme of many cardiovascular abnormalities. This is not surprising, since frequent exposure of blood vessels to excessive hemodynamic stress (eg, hypertension), the noxious effects of blood contents (eg, atherogenic lipids), and locally released cytokines (eg, postangioplasty) require readily available mechanism (s) to counteract their adverse effects and to preserve the intactness of the vessel wall. These responses, which were evolutionarily developed to repair an injured tissue, often escape self-limiting control and result in lumen narrowing. Various vascular lesions contain mesenchymal cells, different from normal medial cells, which has been viewed as evidence that smooth muscle (SM) cells modulate their phenotype in response to changes in the environment in situ. 1 2 3 This concept has been further reinforced by the dedifferentiation of SM cells to a “synthetic” phenotype in culture. 4 The presence of “nonmuscle” cells in the normal vessel wall, however, raises an intriguing question regarding whether they contribute to vascular repair while acquiring markers of muscle differentiation. This review will examine the potential role of these cells in coronary repair and remodeling.

Seminal studies by Gabbiani and coworkers 5 6 have established that wound healing is associated with rapid activation of fibroblasts, which proliferate, migrate, and undergo differentiation to myofibroblasts. These cells acquire bundles of microfilaments (stress fibers) and develop extensive connections with the surrounding extracellular matrix, a change which is consistent with the primary role of newly formed myofibroblasts to close an open wound by means of extracellular matrix protein synthesis and contraction. 7 Subsequent studies have confirmed the pivotal role of myofibroblasts in a wide range of other pathological conditions associated with fibrogenesis and organ remodeling. 8 9 10 11 Although myofibroblasts from such diverse sources are heterogeneous, their common feature is the expression of α-SM actin. 12 When wound healing is completed, myofibroblasts are usually eliminated by apoptosis, 6 except in cases of so-called fibrocontractive disorders, in which their presence is sustained, leading to organ fibrosis and/or constrictive remodeling. 8 13 The ubiquitous formation of myofibroblasts reflects a common mechanism of tissue repair, which raises the fundamental question of whether a similar phenomenon occurs in the vessel wall in response to injury. In the normal artery, nonmuscle cells are primarily found in the adventitia, which also contains vasa vasorum and rich sympathetic innervation. Since activated fibroblasts are notorious for their ability to acquire not only α-SM actin but also several other markers of muscle differentiation, 12 the presence of myofibroblasts in the vessel wall can be easily overlooked and their impact on vascular repair attributed to abundant SM cells.