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Influences of low shear stress flow environments on vascular endothelium: Implications for endothelialization of vascular prostheses
ABSTRACTS
Cardiovasc Pathol Vol. 5, No. 5 September/October 1996:286-302
Rodney A. White,
ENDOLUMINALGRAFTS-CLINICAL APPLICATIONS M.D., Harbor-UCLA Medical Center, Torrance, CA, USA
Endovascular prosthetic treatment of vascular lesions is being Developing performed in many countries with variable monitoring mechanisms. while other investigations are commercial prototypes are being evaluated, being conducted by physicians who assemble devices using commercially In many of the early available vascular stents and vascular prostheses. studies, the feasibility for using this technology to exclude aneurysms and arteriovenous fistulas with short- and intermediate-term success has been demonstrated. Long-term utility of endografts relies upon demonstrating that exclusion of aneurysms fulfills the expectation of decreased morbidity and mortality, lower hospital costs and long-term exclusion of aneurysms and rupture prevention. Endoluminal grafts are also being used to treat The occlusive occlusive vascular lesions with variable success. applications are confronted with more challenging issues because the device must maintain long-term patency similar to conventional bypass procedures. The widespread interest in these technologies has encouraged teams af and cardiologists interventional physicians including surgeons, radiologists to aggressively pursue the evaluation of the endoluminal graft technology. The early indication is that this technique has widespread potential, but the initial enthusiasm must be tempered by limited follow-up of these Improved devices and long-term studies are required to developing methods. insure the eventual safe and widespread application of these methods for the treatment of vascular lesions.
INFLUENCES OF LOW SHEAR ENDOTHELJUM: IMPLICATIONS PROSTHESES Eugene A. Sprague, University
STRESS FLOW ENVSRONMENTS ON VASCULAR FOR ENDOTHELIALIZATION OF VASCULAR of Texas
Health
Science
Center,San
Antonio,TX,
USA
Reendothelialization of the injured arterial wall and endothelialization of prostheses at sites of vascular intervention likely plays a pivotal role in determining the likelihood and extent of acute or longterm restenosis at these sites. The underlying hypothesis of the studies presented here is that the nature of the flow environments either existing at these arterial sites or created by devices implanted may influence both the endothelialization process and the functionality of endothelium at these interventional sites. Using an in vitro flow system to examine the biologic responses of cultured human aortic endothelial cells (HAEC) to defined flow environments, these studies were designed to examine shear stress related influences on monocyte-endothelial cell interactions, an endothelial cell - cell adhesion molecule (EndoCAM,CD31), and endotheliil cell migration rate. Data will be presented demonstrating that HAEC exposed to a prolonged (up to 72h) low shear stress flow regimen exhibited significant19 enhanced monocyte adherence relative to either no flow (NS) or high shear (HS) conditioned HAEC . Further, LS preconditioned HAEC exhibited enhanced expression for two monocyte adhesion genes, monocyte chemotactic protein (MCP-1) and vascular cell adhesion molecule (VCAM-1). Secondly, in studies designed to examine how flow might affect en&the&al cell to cell adhesion a significant time- dependent decrease in EndoCAM gene expression in BAEC exposed to low shear stress for periods beginning at 6h and extending to 72 h relative to cells exposed to either static or high shear flow conditions. Finally, our results indicate that HAEC migration rate and direction directly relates to the intensity and direction of flow-related shear stress. Implication of these results for vascular interventional strategies and device design will be discussed.
297
Cardiovasc Pathol Vol. 5, No. 5 September/October 1996:286-302
Rodney A. White,
ENDOLUMINALGRAFTS-CLINICAL APPLICATIONS M.D., Harbor-UCLA Medical Center, Torrance, CA, USA
Endovascular prosthetic treatment of vascular lesions is being Developing performed in many countries with variable monitoring mechanisms. while other investigations are commercial prototypes are being evaluated, being conducted by physicians who assemble devices using commercially In many of the early available vascular stents and vascular prostheses. studies, the feasibility for using this technology to exclude aneurysms and arteriovenous fistulas with short- and intermediate-term success has been demonstrated. Long-term utility of endografts relies upon demonstrating that exclusion of aneurysms fulfills the expectation of decreased morbidity and mortality, lower hospital costs and long-term exclusion of aneurysms and rupture prevention. Endoluminal grafts are also being used to treat The occlusive occlusive vascular lesions with variable success. applications are confronted with more challenging issues because the device must maintain long-term patency similar to conventional bypass procedures. The widespread interest in these technologies has encouraged teams af and cardiologists interventional physicians including surgeons, radiologists to aggressively pursue the evaluation of the endoluminal graft technology. The early indication is that this technique has widespread potential, but the initial enthusiasm must be tempered by limited follow-up of these Improved devices and long-term studies are required to developing methods. insure the eventual safe and widespread application of these methods for the treatment of vascular lesions.
INFLUENCES OF LOW SHEAR ENDOTHELJUM: IMPLICATIONS PROSTHESES Eugene A. Sprague, University
STRESS FLOW ENVSRONMENTS ON VASCULAR FOR ENDOTHELIALIZATION OF VASCULAR of Texas
Health
Science
Center,San
Antonio,TX,
USA
Reendothelialization of the injured arterial wall and endothelialization of prostheses at sites of vascular intervention likely plays a pivotal role in determining the likelihood and extent of acute or longterm restenosis at these sites. The underlying hypothesis of the studies presented here is that the nature of the flow environments either existing at these arterial sites or created by devices implanted may influence both the endothelialization process and the functionality of endothelium at these interventional sites. Using an in vitro flow system to examine the biologic responses of cultured human aortic endothelial cells (HAEC) to defined flow environments, these studies were designed to examine shear stress related influences on monocyte-endothelial cell interactions, an endothelial cell - cell adhesion molecule (EndoCAM,CD31), and endotheliil cell migration rate. Data will be presented demonstrating that HAEC exposed to a prolonged (up to 72h) low shear stress flow regimen exhibited significant19 enhanced monocyte adherence relative to either no flow (NS) or high shear (HS) conditioned HAEC . Further, LS preconditioned HAEC exhibited enhanced expression for two monocyte adhesion genes, monocyte chemotactic protein (MCP-1) and vascular cell adhesion molecule (VCAM-1). Secondly, in studies designed to examine how flow might affect en&the&al cell to cell adhesion a significant time- dependent decrease in EndoCAM gene expression in BAEC exposed to low shear stress for periods beginning at 6h and extending to 72 h relative to cells exposed to either static or high shear flow conditions. Finally, our results indicate that HAEC migration rate and direction directly relates to the intensity and direction of flow-related shear stress. Implication of these results for vascular interventional strategies and device design will be discussed.
297