Induction of angiotensin converting enzyme in the neointima after vascular injury. Possible role in restenosis.
Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro. Consistent with this, Ang II enhances neointimal proliferation in vivo after vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate this process. Since tissue ACE plays a key role in the control of local Ang II production, we examined whether vascular injury resulted in an increase in vascular ACE expression that may result in increased Ang II production. Abdominal aorta of Sprague-Dawley rats were injured with a 2 French balloon catheter. Morphometrical changes, ACE enzymatic activity, and localization of ACE by immunohistochemistry in injured and uninjured aorta were analyzed. Vascular ACE activity in the injured aorta was significantly higher than in the uninjured aorta, while serum and lung ACE levels were not different between the two groups. The cellular distribution of the ACE protein in the neointima was similar to that of alpha smooth muscle actin but differed from those of endothelial (von Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that ACE was expressed in neointimal smooth muscle cells. These data demonstrate that vascular injury results in the induction of vascular ACE and suggest that the inhibition of vascular ACE may be important in the prevention of restenosis after balloon injury.
Rakugi
H
H
Falk Cardiovascular Research Center, Stanford University School of Medicine, California 94305.
Kim
D K
DK
Krieger
J E
JE
Wang
D S
DS
Dzau
V J
VJ
Pratt
R E
RE
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology; D002404:Catheterization; D004730:Endothelium, Vascular / Q000502:physiology; D004790:Enzyme Induction; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000293:injuries / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis / Q000096:biosynthesis*; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril