Effect of uncoated stenting versus balloon angioplasty alone of long coronary (>20 mm) versus shorter narrowings on one-year event-free survival.
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Biomedical subjects
Publications and source records attributed to Samir R Kapadia.
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We investigated the relation between the presence of matrix-metalloproteinases (MMPs) and direction of remodeling in the coronary lesions of 35 patients. Positive arterial remodeling describes a compensatory expansion of the external elastic membrane (EEM) area of atherosclerotic lesions. An association between positive remodeling and unstable clinical presentation has been previously described. However, the pathophysiology of the remodeling process is not completely understood. Preinterventional intravascular ultrasound images and directional atherectomy (DCA) samples were analyzed. The remodeling ratio was calculated as the EEM area at the lesion site divided by the EEM area at the proximal reference. Positive, intermediate, and negative remodeling were defined as ratios of >1.05, 0.95 to 1.05, and <0.95, respectively. The histologic samples were immunostained for MMP-1, -2, -3, and -9. Positive, intermediate, and negative remodeling was present in 15, 7, and 13 lesions, respectively. Mild and intense cell-associated staining for MMP-1 was found in 21 (68%) and 10 (32%) patients, respectively. Staining for MMP-3 was mild in 20 patients (67%) and intense in 10 patients (33%). Immunostaining for MMP-2 and -9 was mild in all samples. Intense staining for MMP-3 was significantly more common in lesions with positive than negative and/or intermediate remodeling (58% vs 17%; p = 0.04; p = 0.053 after adjustment for gender). Thus, in this in vivo intravascular ultrasound and histologic study, increased cell-associated MMP-3 staining was associated with positive arterial remodeling.
Inflammation has been postulated to contribute to restenosis after balloon angioplasty. Tumor necrosis factor (TNF)-alpha is a pleiotropic proinflammatory cytokine involved in many features of inflammation. We examined the tissue expression pattern of TNF-alpha and the inflammatory response to arterial injury, and the effects of a goat anti-rabbit-TNF-alpha polyclonal antibody on tissue TNF-alpha expression, inflammation and restenosis in a rabbit atherosclerotic model. At different time points following air dessication and subsequent balloon injury, fresh rabbit femoral artery tissues were homogenized and analyzed for TNF-alpha levels by quantitative TNF-alpha bioassay. Rabbits were treated with a goat anti-rabbit-TNF-alpha polyclonal antibody, Serum and tissue TNF-alpha neutralization, macrophage infiltration (as an indicator of inflammation), and neointimal areas were determined. Balloon angioplasty increased tissue TNF-alpha expression 100000-fold over baseline, and this increase persisted over 6 days after arterial injury, serum anti-TNF-alpha antibody levels were sufficient to neutralize tissue TNF-alpha activity by 60-75%, macrophage infiltration was suppressed, but did not decrease the neointimal formation. These data indicate that tissue TNF-alpha levels were markedly increased after balloon angioplasty. Anti-TNF-alpha treatment was sufficient to neutralize tissue TNF-alpha activity, reduce inflammation, but did not inhibit neointimal formation following balloon angioplasty in a rabbit atherosclerotic model.