(Circulation. 1997;95:2684-2693.)
© 1997 American Heart Association, Inc.
Articles |
Remodeling of Autologous Saphenous Vein Grafts
The Role of Perivascular Myofibroblasts
From the Departments of Medicine (Cardiology) (Y.S., W.C., A.F., A.Z.) and Surgery (Cardiothoracic Surgery) (J.E.O., Jr, J.D.M., R.C.M.), Thomas Jefferson University, Philadelphia, Pa.
Correspondence to Andrew Zalewski, MD, Thomas Jefferson University, Cardiovascular Research Center, Division of Cardiology, Suite 410N, 1025 Walnut St, Philadelphia, PA 19107.
Background Aortocoronary saphenous vein grafts (SVGs) undergo structural changes that render them susceptible to atherosclerosis. Accordingly, the origin of neointimal hyperplasia was examined in porcine arterialized SVGs to determine the mechanism of vein graft remodeling.
Methods and Results At 2 to 4 days after surgery, the
percentage of cells lacking differentiation markers characteristic for
smooth muscle (SM) cells (ie, 
-SM actin, desmin, and SM myosin)
increased within the media of SVGs interposed in the carotid arteries
(P<.001). At 7 to 14 days, these cells acquired a
differentiated phenotype (ie, -SM-actin
positive/variable desmin/SM-myosin negative) and accumulated in the
neointima. At 3 months, the neointima was
positive for -SM actin but mostly negative for desmin, which
contrasted with medial SMCs that were invariably positive for -SM
actin, desmin, and SM myosin. To determine the role of nonmuscle cells
in the above process, perivascular wound fibroblasts were selectively
labeled and found to translocate through the media of newly placed
SVGs, contributing to neointimal formation. These migrating
cells differentiated to myofibroblasts exhibiting sustained
-SM-actin expression. The intima of human SVGs, retrieved during
repeat aortocoronary bypass surgery, exhibited the profile of
cytoskeletal proteins that resembled myofibroblasts seen in porcine
SVGs.
Conclusions Perivascular fibroblasts may infiltrate injured
media of arterialized SVGs, differentiate to myofibroblasts
(acquiring -SM actin), and contribute to vein graft remodeling. The
similarities between porcine and human SVGs regarding the repertoire of
cytoskeletal proteins suggest the involvement of myofibroblasts in
graft remodeling in the clinical setting.
Key Words: atherosclerosis • bypass • myofibroblast • remodeling • veins
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