Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall.
The role of caveolae in stretch- versus flow-induced vascular responses was investigated using caveolin 1-deficient [knockout (KO)] mice. Portal veins were stretched longitudinally for 5 min (acute) or 72 h (organ culture). Basal ERK1/2 and Akt phosphorylation were increased in organ-cultured KO veins, as were protein synthesis and vessel wall cross sections. Stretch stimulated acute phosphorylation of ERK1/2 and long-term phosphorylation of focal adhesion kinase (FAK) and cofilin but did not affect Akt phosphorylation. Protein synthesis, and particularly synthesis of smooth muscle differentiation markers, was increased by stretch. These effects did not differ in portal veins from KO and control mice, which also showed the same contractile response to membrane depolarization and inhibition by the Rho kinase inhibitor Y-27632. KO carotid arteries had increased wall cross sections and responded to pressurization (120 mmHg) for 1 h with increased ERK1/2 but not Akt phosphorylation, similar to control arteries. Shear stress by flow for 15 min, on the other hand, increased phosphorylation of Akt in carotids from control but not KO mice. In conclusion, caveolin 1 contributes to low basal ERK1/2 and Akt activity and is required for Akt-dependent signals in response to shear stress (flow) but is not essential for trophic effects of stretch (pressure) in the vascular wall.
Albinsson
Sebastian
S
Vascular Physiology Group, Department of Experimental Medical Science, Lund University, BMC D12, Lund SE-221 84, Sweden. Sebastian.Albinsson@med.lu.se
Nordström
Ina
I
Swärd
Karl
K
Hellstrand
Per
P
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000818:Animals; D002339:Carotid Arteries / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006984:Hypertrophy; D008297:Male; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation; D011169:Portal Vein / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011311:Pressoreceptors / Q000378:metabolism*; D011312:Pressure; D014176:Protein Biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011673:Pulsatile Flow; D011725:Pyridines / Q000494:pharmacology; D013314:Stress, Mechanical; D013997:Time Factors; D014661:Vasoconstriction; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000577:Amides; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D054460:rho-Associated Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3