title: Mechanisms of vein graft atherosclerosis: LDL metabolism and endothelial actin reorganization.
abstract: We have explored the effect of arterial hemodynamics on endothelial cell morphology and low-density lipoprotein metabolism in human saphenous vein segments harvested from tissue donors. An arterial pulsatile perfusion system was used to impose physiologic pressures and flows for 20 hours on saphenous vein and companion (control) femoral artery segments. A venous perfusion apparatus was also employed for the perfusion of a second (control) saphenous vein segment for the same period of time. Calculations of fluid shearing and wall tensile stresses were performed and related to induced changes in endothelial cell geometry and cytoskeletal actin organization and the incorporation, degradation, and localization of intact low-density lipoprotein within the vessel wall. Our results indicate that, compared with native arteries and veins, a 20-hour exposure of test saphenous veins to arterial hemodynamics induced (1) a significant increase in endothelial cell luminal surface area and perimeter independent of alignment with flow, (2) disassembly of the dense peripheral band of actin with a concomitant assembly of stress fibers, and (3) a two- to fourfold elevation in the undegraded low-density lipoprotein content, localized primarily within the subendothelial intima. Although the exact mechanisms underlying these results are uncertain, the focal accumulation of intramural low-density lipoprotein may be related to the loss of normal barrier function during endothelial cell enlargement, which is accompanied by transient cytoskeletal reorganization during the adaptation to arterial flow.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, Pa.
authors.forename: S A
authors.initials: SA
authors.lastname: Berceli
authors.forename: H S
authors.initials: HS
authors.lastname: Borovetz
authors.forename: R A
authors.initials: RA
authors.lastname: Sheppeck
authors.forename: H H
authors.initials: HH
authors.lastname: Moosa
authors.forename: V S
authors.initials: VS
authors.lastname: Warty
authors.forename: M A
authors.initials: MA
authors.lastname: Armany
authors.forename: I M
authors.initials: IM
authors.lastname: Herman
mesh_terms: D000199:Actins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D005263:Femoral Artery / Q000473:pathology / Q000502:physiology; D006083:Graft Occlusion, Vascular / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008955:Models, Cardiovascular; D010477:Perfusion / Q000295:instrumentation; D012501:Saphenous Vein / Q000473:pathology / Q000502:physiology
chemical_list: D000199:Actins; D008077:Lipoproteins, LDL