Asynchronous shear stress and circumferential strain reduces endothelial NO synthase and cyclooxygenase-2 but induces endothelin-1 gene expression in endothelial cells.
OBJECTIVE
Endothelium-derived vasoactive agents NO, endothelin-1 (ET-1), and prostacyclin (PGI2) not only regulate vascular tone but also influence atherogenic processes, including smooth muscle migration and proliferation, as well as monocyte and platelet adhesion. Complex hemodynamics characterized by the temporal phase angle between mechanical factors circumferential strain and wall shear stress (stress phase angle [SPA]) have been implicated in regions prone to pathologic development, such as atherosclerosis and intimal hyperplasia, in coronary and peripheral arteries where the mechanical forces are highly asynchronous (SPA=-180 degrees ). We determined the gene expression of endothelial NO synthase (eNOS), ET-1, and cyclooxygenase-2 (COX-2) affected by asynchronous hemodynamics (SPA=-180 degrees ) relative to normal hemodynamics (SPA=0 degrees ) in bovine aortic endothelial cells.


RESULTS
Quantitative competitive RT-PCR analysis showed that eNOS production (at 5 and 12 hours) and COX-2 production (at 5 hours) were reduced at the gene expression level by asynchronous hemodynamics (SPA=-180 degrees) compared with synchronous hemodynamics (SPA=0 degrees ), whereas ET-1 exhibited an opposite trend (at 5 and 12 hours). NO, ET-1, and PGI2 secretion followed their respective gene expression profiles after 5 and 12 hours.


CONCLUSIONS
Together, these data suggest that highly asynchronous mechanical force patterns (SPA=-180 degrees ) can elicit proatherogenic vasoactive responses in endothelial cells at the gene expression level, indicating a novel mechanism that induces cardiovascular pathology.
Dancu
Michael B
MB
Biomolecular Transport Dynamics Laboratory, Department of Bioengineering, The Pennsylvania State University, Fenske Lab, University Park, USA. dancu@engr.ccny.cuny.edu
Berardi
Danielle E
DE
Vanden Heuvel
John P
JP
Tarbell
John M
JM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D002417:Cattle; D018929:Cell Culture Techniques / Q000295:instrumentation; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D042783:Endothelial Cells / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism*; D019332:Endothelin-1 / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D005786:Gene Expression Regulation / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D013314:Stress, Mechanical; D013997:Time Factors
D019332:Endothelin-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases