Date of Award

1979

Degree Type

Dissertation

Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

George C. Fuller

Abstract

The rate of cell proliferation and the ratio of type I/III collagen synthesized by aorta organ culture and cultured smooth muscle cells (SMC) was determined in cells derived from rabbits with injury induced (daily epinephrine and thyroxine administration) arteriosclerosis and increased vascular collagen synthesis. Tissue was taken from medial smooth muscle of normal and diseased rabbits and incubated in organ or cell culture systems with 2,3- 3H-proline, ascorbate and· beta-aminopropionitrile. Collagen types were separated by SDS-polyacrylamide electrophoresis and CMC-chromatography and quantitated radiometrically. licroscopic observation at 12 days in culture and 3H-thyrnidine incorporation at 18 days in culture indicated a greater rate of proliferation of SMC from explants of arteriosclerotic tissue compared to control. In organ culture the ratio of collagen type III : type I was 1 : 1 in the control group and 1 : 1.7 for the arteriosclerotic group . Collagen type III : type I for daughter cells at the end of the 4th passage was 1 : 1.4 and 1 : 2.0 for control and arteriosclerotic, respectively . By the 10th passage in culture SMC in both groups were synthesizing almost exclusively type I collagen. This study indicates that cells from arteriosclerotic smooth muscle ere fundamentally unique since the ratio of collagen type is controlled by gene expression. This property affecting collagen deposition may play a role in t he pathogenesis of vascular disease.

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