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Effects of Disturbed Flow on Endothelial Cell Function

Institution: University of California, Los Angeles
Investigator(s): Henry Honda, M.D.
Award Cycle: 1995 (Cycle 4) Grant #: 4FT-0358 Award: $52,345
Subject Area: Cardiovascular Disease
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
Atherosclerosis or "hardening of the arteries" is the substrate on which heart attacks and strokes occur. These lesions consistently occur in certain regions of the artery exposed to specific flow patterns. These "predilection sites" are found in regions where flow is slow as well as changing in direction with each heartbeat. The mechanisms by which flow patterns predispose these areas to the development of atherosclerosis are unknown. We have finished construction on a new in vitro model of the artery where artery wall cells can be exposed to these specific flow patterns. This model will enable us to study in further detail the mechanisms by which the development of plaques is affected by flow patterns.

In addition, we have found that monocytes, a type of white blood cell that is found within the inflammatory region of atherosclerotic plaques, produce a factor which significantly increases the intracellular calcium ion levels within two types of artery wall cells, endothelial and smooth muscle cells. The calcium ion levels in these two cell types are known both to regulate the movement of monocytes from the bloodstream into the plaque as well as to control the tone and diameter of blood vessels. Preliminary characterization of the chemical and physical properties of this factor reveals that it is heat-stable and has a molecular weight of less than 10,000. By increasing the calcium levels in artery wall cells, this factor may have an important role in the process of plaque development as well as controlling vascular tone.

Effects of flow on vascular agent-induced increases in endothelial cell calcium
Periodical: Circulation Index Medicus:
Authors: Honda HM, Goldhaber JI, Demer LL, Weiss JN ABS
Yr: 1994 Vol: 90 Nbr: Abs: Pg: I-89

Monocytes produce a soluble factor which stimulates increases in endothelial calcium levels
Periodical: FASEB Journal Index Medicus:
Authors: Honda HM, Goldhaber JI, Weiss JN ABS
Yr: 1995 Vol: 9 Nbr: Abs: Pg: A38