The response of adult human saphenous vein endothelial cells to combined pressurized pulsatile flow and cyclic strain, in vitro.
Adult human saphenous vein endothelial cells (HVEC) were cultured in a compliant tubular device and evaluated by Northern hybridization for the effects of combined pressurized pulsatile flow and cyclic strain on the expression of mRNAs for endothelin-1 (ET-1), endothelial cell nitric oxide synthase (ecNOS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1). The hemodynamic environment was designed to mimic shear stress conditions at the distal anastomosis of a saphenous vein graft, a common site of intimal proliferation. Steady-state mRNA levels in experimental tubes were expressed relative to that in controls. No changes were observed in ET-1 mRNA after 1 and 24 hr, but a 50% decrease in experimental cultures was observed after 48 hr in the vascular simulating device. Similar results were obtained for ecNOS mRNA, although a subgroup (4 of 11) showed a significant decrease (>50%) by 24 hr. For tPA mRNA, no change was observed after 1 hr, but a significant decrease (>60%) was measured after 24 hr and no message was detectable after 48 hr. Steady-state levels for PAI-1 mRNA remained unchanged through 48 hr of treatment. These results show that pressure, pulsatile flow, and cyclic strain, when applied in concert, differentially alter vasoactive and fibrinolytic functions in HVEC. Moreover, the dramatic decrease in steady-state levels of tPA mRNA is consistent with a shift toward an increased thrombotic state.
Tsukurov
O I
OI
Division of Vascular Surgery, Surgical Service, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, MA 02114, USA.
Kwolek
C J
CJ
L'Italien
G J
GJ
Benbrahim
A
A
Milinazzo
B B
BB
Conroy
N E
NE
Gertler
J P
JP
Orkin
R W
RW
Abbott
W M
WM
D000328:Adult; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D011673:Pulsatile Flow; D012333:RNA, Messenger / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism* / Q000637:transplantation; D013314:Stress, Mechanical; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D010959:Tissue Plasminogen Activator