Arterial intimal-medial permeability and coevolving structural responses to defined shear-stress exposures

Abstract

Fry, Donald L. Arterial intimal-medial permeability and coevolving structural responses to defined shearstress exposures. Am J Physiol Heart Circ Physiol 283: H2341-H2355, 2002. First published August 22, 2002 10.1152/ajpheart.00219.2001.-The purpose of this research was to examine the evolution of arterial shear stress-induced intimal albumin permeability and coevolving structural responses in swine arteries. Uniform laminar shear-stress responses were compared with those of a simulated "flow separation" stress field. These fields were created using specially designed flow-configuring devices in an experimentally controlled, metabolically supported, ex vivo thoracoabdominal aorta preparation. The Evans blue dye-albumin complex (EBDalb) permeability patterns that evolved were measured by a reflectometric method. The corresponding tissue structural responses were evaluated by histological, immunostaining, and ultrastructural microscopic techniques. It was shown that when a previously in vivo-adapted artery is challenged by a new mechanochemical environment, it undergoes a sequence of adaptive processes over the ensuing 95 h. Intimal regions of laminar shear-stress exposure (ϳ16 dyn/cm 2 ) responded initially (23 h) with an increase in permeability. With continued stress exposure, intimal-medial structural changes ensued that restored the artery to a physiologically normal permeability. Over this same period, adjacent endothelial regions exposed to simulated flow separation stress fields (ϳ0.03-0.27 dyn/cm 2 ) developed early and progressively increasing permeability. This was associated with formation of local intimal edema, loss of intimal matrix material, and development of distinctively raised, gelatinous-appearing intimal lesions having a potentially preatheromatous architecture.arterial stress adaptation; apoptosis; atheroma; atherosclerosis; endothelial barrier function; flow separation and reattachment phenomenon; porcine artery; gelatinous lesion; laminar shear stress; transendothelial mass transport SINCE THE 1960S, there has been an increasing interest in the effects of various hemodynamic shear-stress exposures on endothelial-intimal permeability, structure (17,21,22), and susceptibility to atherogenesis (4,23,24). Atheroma are slowly developing, raised intimal lesions that are the leading cause of morbidity and death in modern societies. Early studies suggest that hemodynamic factors could influence the endothelial cell surface barrier in an adverse manner to initiate the chain of aberrant interstitial mass transport and cellular events of atherogenesis (2,5,23,27,30). Because one of the initiating events appears to be endothelial barrier failure (3,29,30,42,45), most subsequent work has focused on endothelial cell biology. To do this, special tissue culture systems were developed in which controlled shear stresses could be applied to cultured monolayers of endothelial cells. Endothelial "responses" to these controlled shear-stress exposures were based initially on observations of endothelial cell in...

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