Abstract

This proposal has two overall objectives. The first is to determine how arterial smooth muscle cells respond to different growth promoting or growth inhibiting conditions in vivo. To attain this objective, we will need to develop new approaches for measuring cell kinetic parameters. Methods for measuring cell number, cell cycle times, growth fraction, and cell death will be developed for smooth muscle cells stimulated to proliferate in response to arterial endothelial injury (rat carotid drying model). The differences and similarities of smooth muscle cell behavior under a variety of physiological conditions (acute and chronic hypertention, arterial distension, suppression of growth by heparin) will be studied using these methods. The second objective relates to the observation that the sessel wall, even at rest, contains cells in at least two distict growth states: diploid and tetraploid. Our objective is to examine the ontribution of cells in each of the states to the vessel wall proliferative response. The proposed studies will utilize light and electron microscopy, flow cytometry, Feulgen microdensitometry, cell sorting, and cell culture.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Modified Research Career Development Award (K04)
Project #
5K04HL001108-03
Application #
3073642
Study Section
Pathology A Study Section (PTHA)
Project Start
1983-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Clowes, A W; Clowes, M M; Fingerle, J et al. (1989) Kinetics of cellular proliferation after arterial injury. V. Role of acute distension in the induction of smooth muscle proliferation. Lab Invest 60:360-4
Zacharias, R K; Kirkman, T R; Kenagy, R D et al. (1988) Growth factor production by polytetrafluoroethylene vascular grafts. J Vasc Surg 7:606-10
Hansson, G K; Jonasson, L; Holm, J et al. (1988) Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro. Circ Res 63:712-9
Sprugel, K H; McPherson, J M; Clowes, A W et al. (1988) The effects of different growth factors in subcutaneous wound chambers. Prog Clin Biol Res 266:77-91
Clowes, A W; Clowes, M M; Kocher, O et al. (1988) Arterial smooth muscle cells in vivo: relationship between actin isoform expression and mitogenesis and their modulation by heparin. J Cell Biol 107:1939-45
Sprugel, K H; McPherson, J M; Clowes, A W et al. (1987) Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am J Pathol 129:601-13
Zacharias, R K; Kirkman, T R; Clowes, A W (1987) Mechanisms of healing in synthetic grafts. J Vasc Surg 6:429-36
Clowes, A W; Clowes, M M (1987) Regulation of smooth muscle proliferation by heparin in vitro and in vivo. Int Angiol 6:45-51
Zwolak, R M; Adams, M C; Clowes, A W (1987) Kinetics of vein graft hyperplasia: association with tangential stress. J Vasc Surg 5:126-36
Majesky, M W; Schwartz, S M; Clowes, M M et al. (1987) Heparin regulates smooth muscle S phase entry in the injured rat carotid artery. Circ Res 61:296-300

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