Objective-To validate the hypothesis that the toxic heavy metal lead (Pb) may be linked to cardiovascular diseases via the initiation of atherosclerosis, in vivo and in vitro studies were conducted. Methods and Results-During the human study part of this project, serum Pb levels of healthy young women were correlated to carotid intima-media thickness. Multivariate logistic regression analyses showed that increased serum Pb levels were significantly associated with an increased intima-media thickness (Pϭ0.01; odds ratio per SD unit, 1.6 [95% CI, 1.1 to 2.4]). In vitro, Pb induced an increase in interleukin 8 production and secretion by vascular endothelial cells. Nuclear factor erythroid 2-related factor-2 is the crucial transcription factor involved in Pb-induced upregulation of interleukin 8. Endothelial cell-secreted interleukin 8 triggered intimal invasion of smooth muscle cells and enhanced intimal thickening in an arterial organ culture model. This phenomenon was further enhanced by Pb-increased elastin synthesis of smooth muscle cells. Conclusion-Our data support the hypothesis that Pb is a novel, independent, and significant risk factor for intimal hyperplasia. Key Words: Pb Ⅲ heavy metal Ⅲ endothelial Ⅲ Nrf2 Ⅲ interleukin Ⅲ smooth muscle cell Ⅲ invasion Ⅲ migration Ⅲ vascular Ⅲ pathophysiology Ⅲ risk factor Ⅲ intima media thickness Ⅲ atherosclerosis C ardiovascular and cerebrovascular diseases related to atherosclerosis are the leading cause of death in developed countries. 1 The identification of new risk factors is gaining more and more importance for disease prevention.The toxic heavy metal lead (Pb) is second on the Agency for Toxic Substances and Disease Registry's list of most hazardous substances. 2 Although the environmental burden in most countries has been declining because leaded gasoline is being phased out, 3 sources for Pb uptake are still ubiquitous. For example, Pb is emitted into the air through oil and coal combustion and nonferrous metal production. Pb pipes, Pbsoldered copper pipes, or Pb containing brass joints frequently can be found in older houses 4 and are still an important source for Pb uptake. In developing countries, the recycling of discarded Pb acid batteries under uncontrolled conditions poses a serious problem.The Pb that is absorbed reaches the bloodstream and binds to erythrocytes to an extent of approximately 99%; only 1% of total blood Pb can be found in plasma/serum. The half-life of Pb in blood and soft tissue is short (30 days). However, Pb is deposited in bone (in adults, 94% of the total body burden of Pb is contained in bones and teeth, with a half-life of 27 years 5 ). In addition, Barry 6 found that Pb accumulates in aortal tissue (with concentrations Յ60 mol/L) and that Pb levels in atherosclerotic vessels tend to be higher than in unaffected vessels.In general, blood Pb concentrations of greater than 10 g/dL (ie, Ͼ0.5 mol/L) are defined as Pb poisoning 7 ; however, because of the reported adverse health effects of Pb concentrations less than these values, ...
Our results suggest that UA-mediated inhibition of endothelial VCAM-1 expression reduces the infiltration of venous bypass grafts by CD45-positive cells and inhibits intimal hyperplasia. Apoptosis induction in SMCs may be another method in which UA reduces intimal thickening. UA may constitute a surgery-supportive pharmacon that reduces intimal hyperplasia of vein grafts.
Purpose To test a stent-graft specifically designed for the ascending aorta in phantom, cadaver, and clinical application, and to measure deployment accuracy to overcome limitations of existing devices. Methods A stent-graft has been designed with support wires to fixate the apices toward the inner curvature, thereby eliminating the forward movement of the proximal end which can happen with circumferential tip capture systems. The device was deployed in three aortic phantoms, and in four cadavers, deployment precision was measured. Subsequently, the device was implanted in a patient to exclude a pseudoaneurysm originating from the distal anastomosis after ascending aortic replacement. Results The stent-grafts were successfully deployed in all phantoms and cadavers. Deployment accuracy of the proximal end of the stent-graft was within 1 mm proximally and 14 mm distally to the intended landing zone on the inner curvature, and 2–8 mm distal to the intended landing zone on the outer curvature. In clinical application, the pseudoaneurysm could be successfully excluded without complications. Conclusion The novel stent-graft design promises accurate placement in the ascending aorta. The differential deployment of the apices at the inner and outer curvatures allows deployment perpendicular to the aortic axis. Level of Evidence No level of evidence.
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