Inhibition of atherosclerosis associated with reduction of arterial intramural stress in rabbits.

Thubrikar, Mano J.; Baker, Joseph W.; Nolan, Stanton P.

doi:10.1161/01.atv.8.4.410

Cited by 85 publications

(31 citation statements)

References 22 publications

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“…In contrast, the lack of a clear stretch direction in branch points (70) would not induce the feedback minimization of intracellular stress, and hence JNK activation would be sustained. The differential responses of JNK to uniaxial and biaxial stretches may have significant implications in cellular functions.…”

Section: Ec Response To Cyclic Uniaxial Stretch As a Feedback Controlmentioning

confidence: 97%

Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

Chien¹

2007

American Journal of Physiology-Heart and Circulatory Physiology

762

642

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Chien S. Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell. Am J Physiol Heart Circ Physiol 292: H1209 -H1224, 2007. First published November 10, 2006; doi:10.1152/ajpheart.01047.2006.-Vascular endothelial cells (ECs) play significant roles in regulating circulatory functions. Mechanical stimuli, including the stretch and shear stress resulting from circulatory pressure and flow, modulate EC functions by activating mechanosensors, signaling pathways, and gene and protein expressions. Mechanical forces with a clear direction (e.g., the pulsatile shear stress and the uniaxial circumferential stretch existing in the straight part of the arterial tree) cause only transient molecular signaling of pro-inflammatory and proliferative pathways, which become downregulated when such directed mechanical forces are sustained. In contrast, mechanical forces without a definitive direction (e.g., disturbed flow and relatively undirected stretch seen at branch points and other regions of complex geometry) cause sustained molecular signaling of pro-inflammatory and proliferative pathways. The EC responses to directed mechanical stimuli involve the remodeling of EC structure to minimize alterations in intracellular stress/strain and elicit adaptive changes in EC signaling in the face of sustained stimuli; these cellular events constitute a feedback control mechanism to maintain vascular homeostasis and are atheroprotective. Such a feedback mechanism does not operate effectively in regions of complex geometry, where the mechanical stimuli do not have clear directions, thus placing these areas at risk for atherogenesis. The mechanotransduction-induced EC adaptive processes in the straight part of the aorta represent a case of the "Wisdom of the Cell," as a part of the more general concept of the "Wisdom of the Body" promulgated by Cannon, to maintain cellular homeostasis in the face of external perturbations. feedback; gene expression; Rho GTPase; shear stress; signal transduction; strain ENDOTHELIAL CELLS (ECs), besides being a permeability barrier between the blood and vessel wall, perform many important functions, e.g., cell migration, remodeling, proliferation, apoptosis, and the production, secretion, and metabolism of biochemical substances, as well as the regulation of contractility of vascular smooth muscle cells (SMCs). In addition to their modulations by chemical ligands, ECs respond to mechanical factors, such as fluid shear stress and stretch, which can also be sensed by the EC to modify intracellular signaling, gene expression, and protein expression to result in functional regulations (Fig. 1).The mechanical stresses (forces per unit area, with a unit of dyn/cm 2 ) acting on the vessel wall include the normal and circumferential stresses that result from the action of pressure and the shear stress that acts parallel to the luminal surface of the vessel due to flow (Fig. 2). The circumference stress acts along the vessel wall perimeter to cause stretching. The shear stress acts parallel to the...

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Section: Ec Response To Cyclic Uniaxial Stretch As a Feedback Controlmentioning

confidence: 97%

Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

Chien¹

2007

American Journal of Physiology-Heart and Circulatory Physiology

762

642

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“…8 -10 Indeed, wall stress has been shown to be a biologically relevant stimulus for the development of atherosclerosis. 11 In addition, the cellular components of the arterial wall are exposed to multiple neurohumoral signals that are undoubtedly altered in hypertension. Several lines of evidence have specifically implicated the renin-angiotensin II system in the pathogenesis of atherosclerosis.…”

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confidence: 99%

Angiotensin II–Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice

2001

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Background-Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II-induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. Methods and Results-Angiotensin II (0.7 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 SC) was administered to apoE-deficient mice via osmotic minipumps. The animals were placed on either standard chow or an atherogenic diet. After 8 weeks, the mean atherosclerotic lesion area in the descending thoracic and abdominal aortas of animals on a standard chow diet was 0.4Ϯ0.1% compared with 5.2Ϯ1.2% in those animals maintained on an atherogenic diet (PϽ0.0001). In angiotensin II-treated animals on standard chow, the mean lesion area was increased to 11.0Ϯ2.3%, which was further increased to 69.9Ϯ9.4% (PϽ0.0001) in angiotensin II-treated animals on an atherogenic diet. Similar findings were obtained when tissues from the ascending aorta were analyzed. At 8 weeks in mice receiving a standard chow diet, angiotensin II dramatically increased the atherosclerotic lesion area by 840Ϯ83 m 2 (PϽ0.0001). Animals on a high-fat diet had a similar marked increase in lesion area in response to angiotensin II (217Ϯ19 m 2 , PϽ0.0001). In contrast, when hypertension was induced with norepinephrine, only a modest effect on the atherosclerotic lesion area was observed. Conclusions-Angiotensin II-induced hypertension specifically increased the development of atherosclerosis in apoE knockout mice. This response was seen in animals receiving either standard chow or an atherogenic diet. These studies demonstrate the profound effect of angiotensin II on the development of atherosclerosis.

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“…13 In a separate study, rigid external casts of lesion-prone arteries in normotensive hypercholesterolemic rabbits inhibited plaque formation, perhaps because of reduced wall motion. 14 In the present experiment, we reduced aortic wall motion in the hypertensive atherosclerosis-prone aorta proximal to a coarctation by externally wrapping a segment of aorta and studied the effect on plaque formation.…”

mentioning

confidence: 99%

Reduction of Aortic Wall Motion Inhibits Hypertension-Mediated Experimental Atherosclerosis

Tropea

Schwarzacher

Chang

et al. 2000

ATVB

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Abstract-Hypertension is a well-known risk factor for coronary artery disease and carotid and lower extremity occlusive disease. Surgically induced hypertension in hypercholesterolemic animals results in increased aortic wall motion and increased plaque formation. We tested the hypothesis that reduction in aortic wall motion, despite continued hypertension, could reduce plaque formation. New Zealand White rabbits (nϭ26) underwent thoracic aortic banding to induce hypertension and were fed an atherogenic diet for 3 weeks. In 13 rabbits, a segment of aorta proximal to an aortic band was externally wrapped to reduce wall motion. All animals were fed an atherogenic diet for 3 weeks. Four groups were studied: 1, coarctation control (no wrap, nϭ7); 2, coarctation with loose wrap (nϭ6); 3, coarctation with firm wrap (nϭ7); and 4, control (noncoarcted, nϭ6). Wall motion, blood pressure, and pulse pressure were measured at standard reference sites proximal and distal to the coarctation by use of intravascular ultrasound. Quantitative morphometry was used to measure intimal plaque. Mean arterial pressure and cyclic aortic wall motion were equally increased proximal to the aortic coarctation in all 3 coarcted rabbit groups compared with the control group (PϽ0.001). Wall motion in the segment of aorta under the loose and firm wraps was no different from the control value. The external wrap significantly reduced intimal thickening in the 4 groups by the following amounts: group 1, 0.30Ϯ0.03 mm 2 ; group 2, 0.06Ϯ0.02 mm 2 ; group 3, 0.04Ϯ0.02 mm 2 ; and group 4, 0.01Ϯ0.01 mm 2 (PϽ0.001). Localized inhibition of aortic wall motion in the lesion-prone hypertensive aorta resulted in significant reduction in intimal plaque formation. These data suggest that arterial wall cyclic motion may stimulate cellular proliferation and lipid uptake in experimental atherosclerosis. Key Words: wall motion Ⅲ hypertension Ⅲ atherosclerosis Ⅲ pulse pressure H ypertension is an independent risk factor for coronary artery disease 1,2 and for carotid 3,4 and lower extremity 5,6 occlusive disease. Other multivariate clinical studies have shown that pulse pressure is also an independent risk factor for atherosclerosis. 7,8 Previous experimental studies in our laboratory 9,10 and in others 11,12 have demonstrated that surgically created aortic coarctations increase blood pressure proximal to the coarctation and increase the rate of plaque deposition in hypercholesterolemic rabbits and monkeys.On the other hand, the aorta distal to a severe coarctation experiences reduced wall motion and is largely protected from plaque formation despite hypercholesterolemia in animals. 13 In a separate study, rigid external casts of lesion-prone arteries in normotensive hypercholesterolemic rabbits inhibited plaque formation, perhaps because of reduced wall motion. 14 In the present experiment, we reduced aortic wall motion in the hypertensive atherosclerosis-prone aorta proximal to a coarctation by externally wrapping a segment of aorta and studied the effect on plaq...

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Inhibition of atherosclerosis associated with reduction of arterial intramural stress in rabbits.

Cited by 85 publications

References 22 publications

Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell

Angiotensin II–Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice

Reduction of Aortic Wall Motion Inhibits Hypertension-Mediated Experimental Atherosclerosis

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