Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury.
BACKGROUND
To improve understanding of the cellular basis of the arterial response to injury, we tested whether balloon withdrawal can induce certain inflammatory functions of vascular cells and leukocytes and whether such "activation" persists even after the acute phase of injury.


RESULTS
We examined the expression of several inducible cell surface molecules in the rabbit aorta at 2, 5, 10, and 30 days after balloon injury. Longitudinal sections encompassing parts of the uninjured, border, and injured zones were examined for expression of vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), class II major histocompatibility (MHC) antigens, and markers for smooth muscle cells (SMCs), macrophages, endothelial cells, and T-lymphocytes. Endothelial cell healing involved true endothelial regeneration as well as migration, as shown by nuclear incorporation of bromodeoxyuridine. Luminal endothelial cells at the leading edge of repopulation at each time point expressed VCAM-1. As healing progressed, VCAM-1 expression decreased in the regenerated endothelial cells. The neointimal endothelium also expressed high levels of ICAM-1 that persisted longer than the elevation of VCAM-1. SMCs in the neointima also showed increased levels of ICAM-1. Some neointimal endothelial cells, SMCs, and macrophages also expressed high levels of class II MHC antigens during 30 days after injury.


CONCLUSIONS
Local inflammatory activation of endothelial cells, SMCs, and leukocytes occurs in a predictable sequence and persists up to 30 days after balloon injury to the rabbit aorta. Our findings suggest that ongoing local signals persisting after the original balloon injury may contribute to later phases of intimal thickening.
Tanaka
H
H
Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Longwood Medical Research Center, Boston, MA 02115.
Sukhova
G K
GK
Swanson
S J
SJ
Clinton
S K
SK
Ganz
P
P
Cybulsky
M I
MI
Libby
P
P
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001012:Aorta, Abdominal / Q000293:injuries*; D015815:Cell Adhesion Molecules / Q000032:analysis; D003251:Constriction, Pathologic / Q000473:pathology / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1; D007962:Leukocytes / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000293:injuries*; D011817:Rabbits; D012008:Recurrence; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1