Chapter 5. Responses of the Arterial Wall to Certain Physical Factors

  1. Ruth Porter and
  2. Julie Knight
  1. D. L. Fry

Published Online: 30 MAY 2008

DOI: 10.1002/9780470719954.ch5

Ciba Foundation Symposium 12 - Atherogenesis: Initiating Factors

Ciba Foundation Symposium 12 - Atherogenesis: Initiating Factors

How to Cite

Fry, D. L. (1973) Responses of the Arterial Wall to Certain Physical Factors, in Ciba Foundation Symposium 12 - Atherogenesis: Initiating Factors (eds R. Porter and J. Knight), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470719954.ch5

Author Information

  1. Section on Experimental Atherosclerosis, National Heart and Lung Institute, Bethesda, Maryland

Publication History

  1. Published Online: 30 MAY 2008
  2. Published Print: 1 JAN 1973

ISBN Information

Print ISBN: 9789021940137

Online ISBN: 9780470719954



  • intimal tissue system;
  • arterial wall;
  • plasma proteins;
  • blood flow;
  • connective tissue cells


Detailed study of the topography and varied histological pictures of atherosclerosis suggests that this disease ‘process’ is most usefully viewed as an ensemble of processes that occur in the intimal tissue system in response to a variety of physical and chemical stimuli. Some of the most important of these prccesses are the transport of plasma proteins into the intimal space, intimal fibromuscular hyperplasia, and intimal lipid deposition. It is the purpose of this paper to present the results of a number of studies in which an attempt is made to identify and characterize the dominant parameters controlling these processes. One of the most important parameters is shown to be the mechanical stress that is exerted on the vessel lining by the adjacent blood flow. Depending on the magnitude and stability of the stress pattern, as well as the duration of exposure, certain intinial structural and functional changes occur. These processes have widely diffzring time constants (T.C., the approximate amount of time from the onset of the stress stimulus until a response becomes apparent). The most salient of these stress response processes arid their approximate T.C. may be summarized as follows: (I) Acute exposure of the endothelial surface to an increased mechanical stress is associated with an increased transendothelial flux of protein into the arterial intima (T.C. ∼ minutes). (2) A steady unidirectional shear stress orients the endothelial cells and subjacent connective tissue in the direction of the applied stress (T.C. ∼ weeks to months). (3) Intimal regions chronically exposed to moderately elevated values of unidirectional stress develop intimal fibrosis characterized by a dense, highly oriented, subendothelial collagenous sheet that is sparsely populated with smooth muscle and connective tissue cells (T.C. ∼ months to years). These regions appear to have a decreased permeability to proteins and almost never contain stainable lipid. (4) Intimal regions that appear to be exposed to an unstable stress pattern tend to manifest a more exaggerated intimal thickening characterized by an increased population of smooth muscle and connective tissue cells, poorly oriented collagenous fibres, and a predilection for lipid deposition (T. C. unknown). (5) Endothelial cell erosion occurs in regions exposed to stresses in excess of about 400 dyn/cm2 (T.C. ∼ minutes to hours). (6) Endothelial erosion is followed by an exaggerated reparative response characterized by extraordinary intimal smooth muscle and connective tissue cell proliferation (T.C. ∼ weeks to months).

The relationship of these processes to the maintenance of a hydrodynamically stable conduit system and to the development of atherosclerosis is discussed.