Localization of lipoprotein(a) in a monkey model of rapid neointimal growth.
Lipoprotein(a) [Lp(a)] has been proposed as a restenosis risk factor, but it is not known if Lp(a) is present in the injured arterial wall during the initial neointimal growth. The purpose of this study was to determine if Lp(a) is incorporated into the vessel wall during rapid neointimal formation after arterial injury in primates. In this model, distention of the iliac artery with an angioplasty catheter caused focal breaks in the internal elastic lamina (IEL) in 80% of the vessels and extensive IEL fragmentation with medial disruption in 20% of the vessels. Neointimal growth was noted in all injured arteries; thrombus formation was noted in 40% of the vessels. Based on morphometric measurements, injured arteries had neointimal areas of 0.41 +/- 0.05 (n = 4) and 0.83 +/- 0.23 (n = 6) mm2 at 14 and 28 days after injury, respectively. Control arteries had an intact IEL and a monolayer of intimal cells. Lp(a) localization was examined histologically by using a mouse monoclonal anti-Lp(a) antibody. Lp(a), found in all injured arteries, was localized primarily in the neointima in 50% of the vessels. In the subset of vessels with evidence of thrombus formation, intense Lp(a) immunostaining was associated with the thrombus. Lp(a) was specific to injured arteries as uninjured vessels did not stain. In addition, staining was not seen with a negative control, a nonspecific mouse IgG1 antibody. The presence of Lp(a) at the site of rapid neointimal growth supports a role for this lipoprotein in the response to vascular injury after balloon angioplasty.
Ryan
M J
MJ
Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co, Ann Arbor, Mich 48105, USA. RYANM@aa.wl.com
Emig
L L
LL
Hicks
G W
GW
Ramharack
R
R
Spahr
M A
MA
Kreick
J S
JS
Brammer
D W
DW
Chien
A J
AJ
Keiser
J A
JA
D000818:Animals; D002404:Catheterization; D006965:Hyperplasia; D007083:Iliac Artery / Q000378:metabolism / Q000473:pathology*; D017270:Lipoprotein(a) / Q000032:analysis*; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D017270:Lipoprotein(a)