Injury and repair of endothelium at sites of flow disturbances near abdominal aortic coarctations in rabbits.

Langille, B. Lowell; Reidy, Michael A.; Kline, Robert L.

doi:10.1161/01.atv.6.2.146

Cited by 102 publications

(54 citation statements)

References 20 publications

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“…Endothelial cells showed distinct changes that are known to be induced by elevated WSS, - 40 such as protrusion and increased cell density near the border of desquamation, where a very high WSS was expected, even 8 weeks after operation. However, these changes became indistinct in the proximal segment near the aortic orifice of the same flow-loaded CCA, where elevated WSS was considerably reduced due to luminal dilatation.…”

Section: Discussionmentioning

confidence: 99%

Difference in dilatation between endothelium-preserved and -desquamated segments in the flow-loaded rat common carotid artery.

Tohda

Masuda

Kawamura

et al. 1992

Arterioscler Thromb

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To study arterial dilatation in response to increased flow, we observed the bilateral common carotid arteries (CCAs) of 10 16-week-old rats that were maintained for 8 weeks after construction of an arteriovenous (AV) fistula between the left CCA and the jugular vein at a level 20 mm distal from the aortic orifice. The flow in the left CCA increased 11-fold and that of the right CCA increased twofold compared with values before surgery. The left CCA showed complete desquamation of endothelial cells in the distal one third of the segment proximal to the AV fistula. In the left CCA the endothelium-preserved area dilated significantly (the luminal radius was 134 times larger than control; p<0.001, n=4) with a significant increase of the cross-sectional area of the media (p<0.01, n=4) and showed high wall shear stress (70±ll dynes/cm 1 near the aortic orifice). In contrast, the endothelial cell-desquamated area did not dilate but did show very high wall shear stress (231 ±23 dynes/cm 2 ) without any intimal smooth muscle cell proliferation. The right CCA dilated significantly (luminal radius was 1.07 times larger than control; p<0.001, n=4) with a wall shear stress of 30 dynes/cm 2 near the brachiocephalic orifice. All CCAs retained their fundamental arterial structure. We conclude that in the rat CCA, arterial dilatation in response to increased flow is a gradual remodeling process related to the presence of endothelial cells that have been influenced by the level of flow increase. ( 1 As a long-term response to flow, Kamiya and Togawa, 2 using the arteriovenous (AV) fistula model in the canine carotid artery, suggested that the increased wall shear stress (WSS) induced the adaptive enlargement of the vessel radius, which acted as a negative feedback to reduce the stress itself. Recently Zarins et al, 3 using the AV fistula model, showed a reduction of WSS to baseline level in the flow-loaded iliac artery of cynomolgus monkeys. As a short-term response to flow, Hull et al 4 showed that acute dilatation due to increased flow velocity was endothelium dependent after the endothelial surface of the canine femoral artery was rubbed with a cotton ball. On the other hand, Guyton and Hartley 5 and Langille et al 6 -7 demonstrated that the in vivo reductions in arterial diameter could be induced by a decrease in flow and were endothelium dependent.Our experiments were designed to induce a blood flow increase in the common carotid artery (CCA) by formation of an AV fistula between the left CCA and From the Second Department of Pathology, Akita University School of Medicine, Akita, Japan.Address for reprints: Hirotake Masuda, MD, Second Department of Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010, Japan.Received Jury 8, 1991; revision accepted January 3, 1992.the left external jugular vein in rats; we then observed the morphological changes in the bilateral CCAs after 8 weeks. In this model, because the shunted left CCA showed a marked increase of flow (over 10-fold) and the right contralateral CCA show...

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Section: Discussionmentioning

confidence: 99%

Difference in dilatation between endothelium-preserved and -desquamated segments in the flow-loaded rat common carotid artery.

Tohda

Masuda

Kawamura

et al. 1992

Arterioscler Thromb

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“…65 In addition, in vivo and in vitro studies have suggested that the wall shear stress may influence endothelial recovery after denudation. [66][67][68] Although from these studies, the exact relation between these two factors is not clear. If an extreme deviation of shear stress from normal retards endothelial recovery, this could lessen the inhibitory effect of endothelium and thereby enhance intimal proliferation.…”

Section: Relation Between Low Wall Shear Stress and Intimal Thickeningmentioning

confidence: 99%

Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia.

1989

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Restenosis after successful PTCA remains a major problem limiting the efficacy of the procedure. The pathophysiologic mechanism of restenosis has been enigmatic so far, but accumulated evidence strongly suggests that intimal hyperplasia is the major mechanism. Based on current understanding of the process of intimal hyperplasia, one unifying concept may be that there are at least two major local biologic determinants influencing this process, lesion characteristics and regional flow dynamics. Lesion characteristics include the plaque structure and the quantity of smooth muscle. These may provide the anatomic substrate that determines the extent of injury and the degree of smooth muscle cell proliferation. The amount of smooth muscle cells in the stenotic lesion activated by injury to undergo proliferation may determine the eventual bulk of the restenotic lesion. In addition, low wall shear stress could promote intimal hyperplasia and cause structural change of vessels to decrease the lumen, whereas high wall shear stress exerts the opposite effects. Intimal hyperplasia after balloon injury is a complex process involving platelets, growth factors, endothelial cells, smooth muscle cells, mechanical injury, wall shear stress, and probably other unknown factors. Platelets not only contribute growth factors such as PDGF but also cause organized thrombus. Different growth factors may be involved in initiating smooth muscle cell proliferation and may come from many different sources, including smooth muscle cells, endothelial cells, and macrophages. Intact confluent endothelial cells may produce heparin sulfates and inhibit intimal proliferation; however, regenerating endothelial cells may have the opposite effect. Thus, the proliferative potential of smooth muscle cells, endothelial recovery, extent of injury, wall shear stress, and other unknown factors may all influence this process. Based on these concepts concerning the biology of restenosis, some research directions concerning potential forms of therapy are proposed.

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“…It now is well established that the primary role of hemodynamic forces (mainly shear stress, a frictional force acting at the interface between the flowing blood and the vessel wall), acting through the endothelium, is to cause chronic restructuring of blood vessels (1-6) as well as to initiate blood-vessel formation through a process termed arteriogenesis (7,8). Several in vivo observations suggest that hemodynamic forces modulate endothelial structure and function, which include increased permeability of macromolecules, lipoproteins accumulation, and endothelial cell damage and repair near branch points and bifurcations (2,4,6). More conclusive evidence for the direct effect of hemodynamic forces on endothelial structure and function has come from in vitro studies in which cultured monolayers have been subjected to defined hemodynamic forces in well controlled model systems.…”

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confidence: 99%

VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells

Shay-Salit

Shushy

Wolfovitz

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

300

221

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Blood-flow interactions with the vascular endothelium represents a specialized example of mechanical regulation of cell function that has important physiological and pathophysiological cardiovascular consequences. Yet, the mechanisms of mechanostransduction are not understood fully. This study shows that shear stress induces a rapid induction as well as nuclear translocation of the vascular endothelial growth factor (VEGF) receptor 2 and promotes the binding of the VEGF receptor 2 and the adherens junction molecules, VE-cadherin and ␤-catenin, to the endothelial cytoskeleton. These changes are accompanied by the formation of a complex containing the VEGF receptor 2-VE-cadherin-␤-catenin. In endothelial cells lacking VE-cadherin, shear stress did not augment nuclear translocation of the VEGF receptor 2 and phosphorylation of Akt1 and P38 as well as transcriptional induction of a reporter gene regulated by a shear stress-responsive promoter. These results suggest that VEGF receptor 2 and the adherens junction act as shear-stress cotransducers, mediating the transduction of shearstress signals into vascular endothelial cells.

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Injury and repair of endothelium at sites of flow disturbances near abdominal aortic coarctations in rabbits.

Cited by 102 publications

References 20 publications

Difference in dilatation between endothelium-preserved and -desquamated segments in the flow-loaded rat common carotid artery.

Difference in dilatation between endothelium-preserved and -desquamated segments in the flow-loaded rat common carotid artery.

Restenosis after coronary angioplasty. Potential biologic determinants and role of intimal hyperplasia.

VEGF receptor 2 and the adherens junction as a mechanical transducer in vascular endothelial cells

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