This project will investigate the in vitro cellular senescence of vascular endothelial cells which have been subjected to mechanical forces and its effects on matrix synthesis. Our rationale for these studies is: (1) since atherosclerosis is a major disease involving connective tissue changes whose incidence is significantly higher in older individuals, and since the major cell types affected are endothelial and smooth muscle cells, it is appropriate to determine the relation between matrix synthesis and aging, (2) atherosclerotic changes occur over a long time frame (years) and our system will permit us to model this time frame in vitro, and (3) the mechanism by which mechanical stimulation may affect cell metabolism and protein synthesis remains to be elucidated. In the present study, we plan to utilize vascular cells to examine several other specialized functions of endothelium. We will investigate the rate of synthesis of matrix proteins such as collagen and fibronectin. In addition, we will investigate the effects of mechanical forces on these rates throughout their replicative life-span. We will also determine if application of mechanical forces alters the in vitro life-span of these cells. We will also determine if a redistribution of matrix components occurs in mechanically strained or stressed cells by using immunohistochemistry. Light and electron microscopic studies will be carried out to evaluate these changes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034005-05
Application #
3346486
Study Section
Pathology A Study Section (PTHA)
Project Start
1985-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University City Science Center
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Chaqour, B; Howard, P S; Macarak, E J (1999) Identification of stretch-responsive genes in pulmonary artery smooth muscle cells by a two arbitrary primer-based mRNA differential display approach. Mol Cell Biochem 197:87-96
Chaqour, B; Howard, P S; Richards, C F et al. (1999) Mechanical stretch induces platelet-activating factor receptor gene expression through the NF-kappaB transcription factor. J Mol Cell Cardiol 31:1345-55
Cargill 2nd, R S; Thibault, L E (1996) Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural trauma. J Neurotrauma 13:395-407
Baskin, L S; Constantinescu, S; Duckett, J W et al. (1994) Type III collagen decreases in normal fetal bovine bladder development. J Urol 152:688-91
Baskin, L; Meaney, D; Landsman, A et al. (1994) Bovine bladder compliance increases with normal fetal development. J Urol 152:692-5;discussion 696-7
Winston, F K; Thibault, L E; Macarak, E J (1993) An analysis of the time-dependent changes in intracellular calcium concentration in endothelial cells in culture induced by mechanical stimulation. J Biomech Eng 115:160-8
Baskin, L S; Constantinescu, S C; Howard, P S et al. (1993) Biochemical characterization and quantitation of the collagenous components of urethral stricture tissue. J Urol 150:642-7
Baskin, L; Howard, P S; Macarak, E (1993) Effect of physical forces on bladder smooth muscle and urothelium. J Urol 150:601-7
Baskin, L S; Howard, P S; Duckett, J W et al. (1993) Bladder smooth muscle cells in culture: I. Identification and characterization. J Urol 149:190-7
Baskin, L; Howard, P S; Macarak, E (1993) Effect of mechanical forces on extracellular matrix synthesis by bovine urethral fibroblasts in vitro. J Urol 150:637-41

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