PMID- 19969080
OWN - NLM
STAT- MEDLINE
DCOM- 20100712
LR  - 20131121
IS  - 1569-1802 (Electronic)
IS  - 0945-053X (Linking)
VI  - 29
IP  - 3
DP  - 2010 Apr
TI  - Imbalance between matrix metalloproteinases and tissue inhibitor of 
      metalloproteinases in hypertensive vascular remodeling.
PG  - 194-201
LID - 10.1016/j.matbio.2009.11.005 [doi]
AB  - Structural vascular changes in two-kidney, one-clip (2K-1C) hypertension may 
      result from increased matrix metalloproteinase (MMP)-2 activity. MMP-2 activation 
      is regulated by other MMPs, including transmembrane-MMPs, and by tissue 
      inhibitors of MMPs (TIMPs). We have investigated the localization of MMP-2, -9, 
      -14, and TIMPs 1-4 in hypertensive aortas and measured their levels by 
      zymography/Western blotting and immunohistochemistry. Gelatinolytic activity was 
      assayed in tissues by in situ zymography. Sham-operated and 2K-1C hypertensive 
      rats were treated with doxycycline (or vehicle) for 8 weeks, and the systolic 
      blood pressure was monitored weekly. Doxycycline attenuated 2K-1C hypertension 
      (165 + or - 11.7 mmHg versus 213 + or - 7.9 mm Hg in hypertensive controls, 
      P<0.01), and completely prevented increase in the thicknesses of the media and 
      the intima in 2K-1C animals (P<0.01). Increased amounts of MMP-2, -9, and -14 
      were found in hypertensive aortas, as well as enhanced gelatinolytic activity. A 
      gradient in the localization of MMP-2, -9, and -14 was found, with increased 
      amounts detected in the intima, at sites with higher gelatinolytic activity. 
      Doxycycline attenuated hypertension induced increases in all the 3 investigated 
      MMPs in both the media and the intima (all P<0.05), but it did not change the 
      amounts of TIMPs 1-4 (P>0.05). Therefore, an imbalance between increased amounts 
      of MMPs at the tissue level without a corresponding increase in the quantities of 
      TIMPs, particularly in the intima and inner media layers, appears to account for 
      the increased proteolytic activity found in 2K-1C hypertension-induced 
      maladaptive vascular remodeling.
CI  - Copyright 2009 Elsevier B.V. All rights reserved.
FAU - Castro, Michele M
AU  - Castro MM
AD  - Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, Brazil.
FAU - Rizzi, Elen
AU  - Rizzi E
FAU - Prado, Cibele M
AU  - Prado CM
FAU - Rossi, Marcos A
AU  - Rossi MA
FAU - Tanus-Santos, Jose E
AU  - Tanus-Santos JE
FAU - Gerlach, Raquel Fernanda
AU  - Gerlach RF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091205
PL  - Netherlands
TA  - Matrix Biol
JT  - Matrix biology : journal of the International Society for Matrix Biology
JID - 9432592
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - N12000U13O (Doxycycline)
SB  - IM
MH  - Animals
MH  - Aorta/metabolism/pathology
MH  - Blood Pressure/physiology
MH  - Blotting, Western
MH  - Doxycycline/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Matrix/*metabolism
MH  - Hypertension/embryology/*metabolism/pathology
MH  - Immunohistochemistry
MH  - Male
MH  - Matrix Metalloproteinases/*metabolism
MH  - Organ Size/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
MH  - Tunica Intima/metabolism/ultrastructure
EDAT- 2009/12/09 06:00
MHDA- 2010/07/14 06:00
CRDT- 2009/12/09 06:00
PHST- 2009/09/04 00:00 [received]
PHST- 2009/11/30 00:00 [revised]
PHST- 2009/11/30 00:00 [accepted]
PHST- 2009/12/09 06:00 [entrez]
PHST- 2009/12/09 06:00 [pubmed]
PHST- 2010/07/14 06:00 [medline]
AID - S0945-053X(09)00185-1 [pii]
AID - 10.1016/j.matbio.2009.11.005 [doi]
PST - ppublish
SO  - Matrix Biol. 2010 Apr;29(3):194-201. doi: 10.1016/j.matbio.2009.11.005. Epub 2009 
      Dec 5.