Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels.
BACKGROUND
Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins.


METHODS
Unused portions of human saphenous vein and radial artery were obtained fresh at the time of peripheral or coronary bypass. A sample of the vessel was immediately snap frozen (control(0)) and the remainder separated into three segments. One segment was placed in sterile medium and left undisturbed for 2 h (control(2)), one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min, yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment, samples were tested for phosphorylated ERK1/2 and JNK using Western blot.


RESULTS
Two hours of culture produced mild increases in ERK1/2 activity in both vessel types. Stimulation with continuous rapid flow produced significantly increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static pressurization also stimulated ERK1/2, although slightly less than continuous flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial arteries, and exposure to normal systemic pressure showed no appreciable effect. Significant phosphorylation of JNK was not observed in either vessel.


CONCLUSIONS
ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries exposed to the hemodynamic conditions of arterial grafting. This pathway may be involved in the transduction of external stimuli leading to remodeling.
Curi
Michael A
MA
Section of Vascular Surgery, Department of Surgery, University of Chicago, Illinois 60637, USA.
Skelly
Christopher L
CL
Meyerson
Shari L
SL
Baldwin
Zachary K
ZK
Lee
Eric
E
Lanahan
Jill
J
Jayakar
David
D
Bassiouny
Hisham S
HS
Schwartz
Lewis B
LB
D003470:Culture Media; D004789:Enzyme Activation / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010477:Perfusion; D011312:Pressure; D017534:Radial Artery / Q000502:physiology*; D012501:Saphenous Vein / Q000502:physiology*; D013314:Stress, Mechanical
D003470:Culture Media; D020928:Mitogen-Activated Protein Kinases