Abstract-Nonlaminar flow is a major predisposing factor to atherosclerosis. Yet little is known regarding hemodynamic gene regulation in disease-prone areas of the vascular tree in vivo. We have determined spatial patterns of expression of endothelial cell receptors in the arterial tree and of reporter gene constructs in transgenic animals. In this study we show that the endothelial cell-specific receptor Tie1 is induced by disturbed flow in atherogenic vascular niches. Specifically, tie1 expression in the adult is upregulated in vascular bifurcations and branching points along the arterial tree. It is often confined to a single ring of endothelial cells functioning as sphincters and hence experiencing the steepest gradient in shear stress. In aortic valves, tie1 is asymmetrically induced only in endothelial cells encountering changes in flow direction. Disturbance of laminar flow by a surgical interposition of a vein into an artery led to induction of tie1, specifically in the region where the differently sized vessels adjoin. In pathological settings, tie1 expression is specifically induced in areas of disturbed flow because of the emergence of aneurysms and, importantly, in endothelial cells precisely overlying atherosclerotic plaques. Hemodynamic features of atherosclerotic lesion-prone regions, recreated in vitro with the aid of a flow chamber with a built-in step, corroborated an upregulated tie1 promoter activity only in cells residing where flow separation and recirculation take place. These defined promoter elements might be harnessed for targeting gene expression to atherosclerotic lesions. Key Words: angiogenesis Ⅲ atherosclerosis Ⅲ basic research Ⅲ blood flow Ⅲ blood vessels T he luminal surface of blood vessels is constantly exposed to hemodynamic forces, primarily to shear stress that is the tangential force engendered on endothelial cell surfaces by the blood flow. Hemodynamic forces play a fundamental remodeling role in the vascular network during its formative stage as well as in adapting the adult vasculature to pathophysiological changes in shear stress (eg, the process of arteriogenesis 1 ). Hemodynamic forces are also a considerable factor in the development of vascular pathologies such as atherosclerosis, aneurysms, poststenotic dilatations, and arteriovenous malformations. Notably, these diseases have the propensity to develop in vascular regions distinguished by disturbed flow that occurs naturally in certain vascular niches. Atherosclerosis, although clearly associated with some systemic risk factors, is a geometrically focal disease that preferentially develops at the outer edges of blood vessel bifurcations and at points of blood flow recirculation and stasis (eg, in aortic valves). In these predisposed locations, fluid shear stress on the vessel wall is significantly lower in magnitude and exhibits directional changes and flow separation, features absent from regions of the vascular tree generally spared from atherosclerosis. 2 The detrimental effects of disturbed flow have inspired e...
The simplified sleeve gastrectomy is a technically straightforward, low-mortality technique for creating a bariatric mouse model which most faithfully replicates bariatric surgery performed in humans. This model can be a valuable tool to investigate the glucose tolerance and beta cell effects of bariatric surgery.
The preferred treatment for penetrating neck injuries has changed over the last decade as availability of agile CT scanners has reduced the necessity for routine neck exploration. 10,13 The ability to assess and treat patients with penetrating injuries within an adequate timetable is a challenge especially under the circumstances of a mass casualty event. 5,12 A critically wounded 23-year-old woman was one of numerous passengers injured by shrapnel and blast during a suicide terror attack on a bus. Spiral CT and formal angiography revealed bilateral common carotid perforating injuries and false aneurysm at the origin of the innominate artery. The intraoperative findings also included right internal jugular vein transection and lateral tear of the left internal jugular vein. These injuries were repaired by a multidisciplinary surgical team approach using various reconstructive techniques. Case reportOn 21st November 2002, a suicide bomber detonated an explosive device inside a bus in very close proximity to the Hadassah Hebrew University Medical Center. Fifty-eight civilians were wounded and 10 were killed on site. Forty-four of these were transferred to the trauma unit over a time span of 26 min from the explosion. After the first triage, 15 patients were admitted to the hospital, 6 of whom were rushed to the operating suite and operated on simultaneously. Five patients required surgical intervention over the next 4 hours. One patient suffering a penetrating neck injury, died in surgery.Another of the casualties, a 23-year-old woman, was still awake and responsive upon arrival. She was
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.