BACKGROUND: High blood pressure causes a change in vascular wall structure involving altered extracellular matrix composition, but how this process occurs is not fully understood. METHODS AND RESULTS: Using mouse carotid arteries maintained in organ culture for 3 days, we detected increased gelatin zymographic activity of matrix metalloproteinase (MMP)-2 (168+/-13%, P<0.05) in vessels kept at low intraluminal pressure (10 mm Hg) compared with vessels at 80 mm Hg (100%), whereas in vessels maintained at high pressure (150 mm Hg), both MMP-2 and MMP-9 activity was induced (182+/-32%, P<0.05, and 194+/-21%, P<0.01, respectively). MMPs were detected in endothelial and smooth muscle cells by immunohistochemistry and in situ gelatin zymography. In vessels at 150 mm Hg, MMP activation was associated with a shift in the pressure-diameter curve toward greater distensibility (P<0.01) compared with vessels at 80 mm Hg. However, distensibility was not altered in vessels at 10 mm Hg, in which only activated MMP-2 was detected. The role of MMPs in high pressure-induced vessel distensibility was confirmed by use of the MMP inhibitor FN-439, which prevented the shift in the pressure-diameter relationship. Furthermore, in carotid arteries from MMP-9-deficient mice, the pressure-dependent increase in MMP-2 and in situ gelatinolytic activity were maintained, but the upward shift in the pressure-diameter curve was abolished. CONCLUSIONS: MMP-9 seems to play a key role in the early stages of hypertensive vascular remodeling.
BACKGROUND: High blood pressure causes a change in vascular wall structure involving altered extracellular matrix composition, but how this process occurs is not fully understood. METHODS AND RESULTS: Using mouse carotid arteries maintained in organ culture for 3 days, we detected increased gelatin zymographic activity of matrix metalloproteinase (MMP)-2 (168+/-13%, P<0.05) in vessels kept at low intraluminal pressure (10 mm Hg) compared with vessels at 80 mm Hg (100%), whereas in vessels maintained at high pressure (150 mm Hg), both MMP-2 and MMP-9 activity was induced (182+/-32%, P<0.05, and 194+/-21%, P<0.01, respectively). MMPs were detected in endothelial and smooth muscle cells by immunohistochemistry and in situ gelatin zymography. In vessels at 150 mm Hg, MMP activation was associated with a shift in the pressure-diameter curve toward greater distensibility (P<0.01) compared with vessels at 80 mm Hg. However, distensibility was not altered in vessels at 10 mm Hg, in which only activated MMP-2 was detected. The role of MMPs in high pressure-induced vessel distensibility was confirmed by use of the MMP inhibitor FN-439, which prevented the shift in the pressure-diameter relationship. Furthermore, in carotid arteries from MMP-9-deficient mice, the pressure-dependent increase in MMP-2 and in situ gelatinolytic activity were maintained, but the upward shift in the pressure-diameter curve was abolished. CONCLUSIONS:MMP-9 seems to play a key role in the early stages of hypertensive vascular remodeling.
Authors: Robert C Kaplan; Elizabeth Sinclair; Alan L Landay; Nell Lurain; A Richey Sharrett; Stephen J Gange; Xiaonan Xue; Christina M Parrinello; Peter Hunt; Steven G Deeks; Howard N Hodis Journal: Atherosclerosis Date: 2011-03-15 Impact factor: 5.162
Authors: Li Lei; Dinggang Liu; Yan Huang; Ion Jovin; Shaw-Yung Shai; Themis Kyriakides; Robert S Ross; Frank J Giordano Journal: Mol Cell Biol Date: 2007-11-05 Impact factor: 4.272
Authors: Diogo M O Marçal; Elen Rizzi; Alisson Martins-Oliveira; Carla S Ceron; Danielle A Guimaraes; Raquel F Gerlach; Jose E Tanus-Santos Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2010-10-31 Impact factor: 3.000