Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries.
BACKGROUND
In the present series of experiments, we examined the onset of cell proliferation and growth factor expression after balloon overstretch injury to porcine coronary arteries.


RESULTS
Domestic juvenile swine underwent balloon overstretch injury to the left anterior descending and circumflex coronary arteries with standard percutaneous transluminal coronary angioplasty balloon catheters. To identify proliferating cells, 5-bromo-2-deoxyuridine (BrDU) was administered over a period of 24 hours before the animals were killed at either 1, 3, 7, or 14 days after injury. Immunohistochemistry was performed with monoclonal antibodies to BrDU and smooth muscle cell markers. Three days after injury, a large number of proliferating cells were located in the adventitia, with significantly fewer positive cells found in the media and lumen. Seven days after injury, proliferating cells were found primarily in the neointima, extending along the luminal surface. In situ hybridization for PDGF A-chain and beta-receptor mRNAs revealed that the expression of these two genes was closely correlated with the sites of proliferation at each time point. Studies in which BrDU was injected between days 2 and 3 and the animals were killed on day 14 suggested that the proliferating adventitial cells may migrate into the neointima.


CONCLUSIONS
These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.
Scott
N A
NA
Department of Medicine, Emory University, Atlanta, Ga 30322, USA.
Cipolla
G D
GD
Ross
C E
CE
Dunn
B
B
Martin
F H
FH
Simonet
L
L
Wilcox
J N
JN
D000818:Animals; D001483:Base Sequence; D001973:Bromodeoxyuridine; D002404:Catheterization; D002455:Cell Division; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology / Q000502:physiology*; D005260:Female; D007150:Immunohistochemistry; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D013552:Swine; D017539:Tunica Intima / Q000293:injuries* / Q000473:pathology / Q000502:physiology*; D014949:Wounds, Nonpenetrating / Q000209:etiology*
D015335:Molecular Probes; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor; D001973:Bromodeoxyuridine