Letter by Lee Regarding Article, “CC Chemokine Receptor-1 Activates Intimal Smooth Muscle–Like Cells in Graft Arterial Disease”
To the Editor:
Shimizu et al have made further contributions toward the understanding of graft arterial disease, highlighted by their latest finding of CC chemokine receptor-1 involvement in the activation of intimal smooth muscle–like cells in this disease entity.1 In this article, the authors made a clear distinction between intimal and medial smooth muscle cells based on numerous important functional differences and refer to the intimal smooth muscle cells as smooth muscle–like cells.1
I am interested in whether the authors have considered the possible correlation between smooth muscle–like cells and fibrocytes. Fibrocytes were first described by Bucala et al2 in 1994: “for the first time a population of circulating cells with fibroblast properties that specifically enter sites of tissue injury. This novel cell type, termed a fibrocyte, was characterized by its distinctive phenotype (collagen+/vimentin+/CD34+), by its rapid entry from blood into subcutaneously implanted wound chambers, and by its presence in connective tissue scars.”
Similar to the smooth muscle–like cells described by the authors, fibrocytes are also spindle shaped. They too express typical smooth muscle cell markers such as calponin and smooth muscle α-actin, but more specifically are characterized by expression of procollagen and leukocyte specific protein-1. Under electron microscopy, fibrocytes differ from stromal fibroblasts with the presence of an elongated body with a cluster of fiber-like projections at one end and numerous blebs on the surface of the cell body. In contrast, fibroblasts have a smooth cell body and only a single retraction fiber.3
Fibrocytes have subsequently been recognized to be involved in many disease processes, including neointimal formation (previously known as intimal hyperplasia). Varcoe et al4 demonstrated the contribution of fibrocytes in intimal hyperplasia using an ovine carotid artery patch graft model and supported the view of a bone marrow origin of fibrocytes. Neointimal formation observed after arterial surgery is similar in nature to graft arterial disease and is a major obstacle to the longevity of any type of arterial intervention.
The role of CC chemokine receptor-2 in the regulation of recruitment and activation of fibrocytes to the alveolar space after fibrotic injury has also been previously reported by Moore et al.5 This paralleled strongly with the discovery by Shimizu et al of CC chemokine receptor-1 activation of smooth muscle–like cells.
The similarities between smooth muscle–like cells and fibrocytes warrant further exploration; within may lie a link between these hitherto disparate disease processes.
Shimizu K, Minami M, Shubiki R, Lopez-Ilasaca M, MacFarlane L, Asami Y, Li Y, Mitchell RN, Libby P. CC chemokine receptor-1 activates intimal smooth muscle–like cells in graft arterial disease. Circulation. 2009; 120: 1800–1813.
Bucala R. Fibrocytes: New insights Into Tissue Repair and Systemic Fibrosis. 1st ed. Singapore: World Scientific Publishing Co Pte Ltd; 2007.