Hemodynamics and the vascular endothelial cytoskeleton.

Abstract

Abstract, Although there is considerable evidence to suggest that hemodynamics play an important role in vascular disease processes, the exact mechanisms are unknown. With this in mind, we have designed a pulsatile perfusion apparatus which reproducibly delivers pulsatile hemodynamics upon freshly excised canine carotid arteries in vitro. Quantifiable simulations included (a) normotension with normal or lowered flow rates (120/80 mmHg, 120 and 40 ml/min), (b) normotension with lowered or elevated transmural pressures (40-170 mmHg), and (c) elevated pulse pressure (120 and 80 mmHg) with normal (150 ml/min) or elevated rates of flow (300 and 270 ml/min). Arterial biomechanical stresses and cellular behaviors were characterized biochemically and morphologically under all these simulations which continued for 2-24 h. We found that increased pulse pressure alone had little effect on the total amount of radiolabeled [4-J4C]cholesterol present within the medial compartment. However, normotension when coupled with altered transmural pressure yielded a three-to fourfold increase.Combinations of increased pulse pressure and flow potentiated cholesterol uptake by a factor of 10 when compared with normotension control values. Simulations that enhanced carotid arterial cholesterol uptake also influenced the endothelial cytoskeletal array of actin. Stress fibers were not present within the carotid endothelial cells of either the sham controls or the normotension and increased pulse pressure (normal flow) simulations. Endothelial cells lining carotids exposed to elevations in flow or those present within vessels perfused as per simulation b above assembled stress fibers (x = 4 and 10 per cell, respectively) within the time course of these studies. When endothelial cells were subjected to hemodynamic conditions that potentiated maximally cholesterol transport, no diffuse or stress fiber staining could be seen, but the cortical array of actin was intact. These results suggest that those biomechanical stresses that alter endothelial permeability and intimal integrity may do so via cytoskeletal actin signaling.ECENT experimental evidence indicates that endothelial cells (EC), 1 which line the blood vascular systems of higher vertebrates, are actively involved in maintenance of intimal integrity. This stabilization against the blood shearing forces and biomechanical wall stresses at the luminal-EC interface may be directly related to the intimal cells' ability to synthesize and organize (a) junctional elements, (b) materials of the basal laminae that promote EC adhesion to the extracellular matrix, and (c) an intricate cytoskeleton composed of contractile and structural proteins needed to modulate the luminal-abluminal shear zone.Early work in vitro revealed that vascular EC possessed linear cytoplasmic fibrils (16). Naming the structures "tension striae" the Lewises proposed that these elements (later renamed "stress fibers") promoted adhesion of cells to the underlying substrate. A structural rather than motile role for stress fi...

The morphology of valves and valve-like structures in the canine and feline thoracic duct

“…It is widely accepted that actin filaments are responsible for the cells' attachment to the substrate (Franke et al 1984;Herman et al 1987). However, in the present study we observed an accumulation of the intermediate-sized filaments in the cells situated in unfavorable lymphodynamic conditions, with increased shear stress, whereas the stress fibers to which up to now, cell adhesion has been assigned were not detected.…”

Patterns of Internal Elastic Lamina Morphology in the Canine Common Carotid Artery

“…The subendothe-Hal structures, however, were not as clearly defined as in the present specimens. Exami nation of published SEMs, however, shows that 1EL fenestra can be seen in other prepa rations with intact endothelium [Herman et al, 1987, fig. 9a], It may be, that these struc tures are more prominent in the present specimens because of the method of fixation.…”

Investigation of hemodynamics in the development of dissecting aneurysm within patient-specific dissecting aneurismal aortas using computational fluid dynamics (CFD) simulations

“…Besides family history and genetic factors, there are several mechanical factors that can affect the onset, generation and progression of dissecting aneurysm, including hemodynamics (Herman et al, 1987;Blanco et al, 2006;Feijoo, 2009), vascular geometry (Feijoo, 2009), mechanical properties and composition of the aorta wall (Feijoo, 2009). However, hemodynamics is believed to play a key role in the formation and the progression of the dissecting aneurysm (Herman et al, 1987).…”