Although research in atherosclerosis has focused on mechanisms of initiation, relatively little attention has been given to the more pressing problems of disease progression and recurrence after vascular reconstruction. There are two major objectives in the SCOR: to develop an understanding of how carotid atherosclerotic plaques enlarge and at a certain point become the cause of thromboembolic events; and to explore various aspects of the reparative response and the recurrence of lumenal narrowing after endarterectomy. Four of the projects will examine ultrasound characteristics of advanced atherosclerotic carotid and femoral lesions and endarterectomy-induced intimal thickening. These will be correlated with clinical symptoms and with the pathological characteristics of the excised surgical specimens. In addition, these lesions will be examined by in situ hybridization and Northern analysis for the expression of specific genes important for smooth muscle growth. Magnetic resonance imaging studies will be undertaken in vitro and in vivo model systems to develop better methods for the morphological and biochemical characterization of the human plaque. At the same time, animal models of disease progression and recurrent stenosis will be developed to define factors regulating smooth muscle proliferation and endothelial regeneration. In addition to an Administrative Core, the SCOR will have Morphology an? Image Analysis Cores to provide histological, immunocytological, and image procession support for the individual projects. The proposed studies will make use of a wide range of clinical basic research approaches, including ultrasound, MRI, light and electron microscopy, in situ hybridization, Norther analysis, analysis of cell cycle kinetics and modern approaches to growth factor biochemistry.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL042270-04
Application #
3106848
Study Section
Special Emphasis Panel (SRC (SL))
Project Start
1990-01-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
O'Brien, E R; Urieli-Shoval, S; Garvin, M R et al. (2000) Replication in restenotic atherectomy tissue. Atherosclerosis 152:117-26
Gilja, O H; Detmer, P R; Jong, J M et al. (1997) Intragastric distribution and gastric emptying assessed by three-dimensional ultrasonography. Gastroenterology 113:38-49
Beach, K W; Comess, K A; Primozich, J F et al. (1997) Ultrasonic color flow mapping: the visualization of four-dimensional cardiac and vascular flow phenomena using two dimensions and ""real time"". Ultrasound Med Biol 23:347-63
Hatsukami, T S; Ferguson, M S; Beach, K W et al. (1997) Carotid plaque morphology and clinical events. Stroke 28:95-100
Isik, F F; Coughlin, S R; Nelken, N A et al. (1996) JE gene expression in an animal model of acute arterial graft rejection. J Surg Res 60:224-31
Papanicolaou, G; Beach, K W; Zieler, R E et al. (1996) Systolic flow limitation in stenotic lower-extremity vein grafts. J Vasc Surg 23:394-400
Murry, C E; Bartosek, T; Giachelli, C M et al. (1996) Platelet-derived growth factor-A mRNA expression in fetal, normal adult, and atherosclerotic human aortas. Analysis by competitive polymerase chain reaction. Circulation 93:1095-106
Isik, F F; Rand, R P; Gruss, J S et al. (1996) Monocyte chemoattractant protein-1 mRNA expression in hemangiomas and vascular malformations. J Surg Res 61:71-6
deBlois, D; Viswanathan, M; Su, J E et al. (1996) Smooth muscle DNA replication in response to angiotensin II is regulated differently in the neointima and media at different times after balloon injury in the rat carotid artery. Role of AT1 receptor expression. Arterioscler Thromb Vasc Biol 16:1130-7
O'Brien, E R; Bennett, K L; Garvin, M R et al. (1996) Beta ig-h3, a transforming growth factor-beta-inducible gene, is overexpressed in atherosclerotic and restenotic human vascular lesions. Arterioscler Thromb Vasc Biol 16:576-84

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