PMID- 18065523
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20211020
IS  - 0363-6135 (Print)
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 294
IP  - 2
DP  - 2008 Feb
TI  - Interruption of endothelin signaling modifies membrane type 1 matrix 
      metalloproteinase activity during ischemia and reperfusion.
PG  - H875-83
AB  - The matrix metalloproteinases (MMPs), in particular, membrane type 1 MMP 
      (MT1-MMP), are increased in the context of myocardial ischemia and reperfusion 
      (I/R) and likely contribute to myocardial dysfunction. One potential upstream 
      induction mechanism for MT1-MMP is endothelin (ET) release and subsequent protein 
      kinase C (PKC) activation. Modulation of ET and PKC signaling with respect to 
      MT1-MMP activity with I/R has yet to be explored. Accordingly, this study 
      examined in vivo MT1-MMP activation during I/R following modification of ET 
      signaling and PKC activation. With the use of a novel fluorogenic microdialysis 
      system, myocardial interstitial MT1-MMP activity was measured in pigs (30 kg; n = 
      9) during I/R (90 min I/120 min R). Local ET(A) receptor antagonism (BQ-123, 1 
      microM) and PKC inhibition (chelerythrine, 1 microM) were performed in parallel 
      microdialysis probes. MT1-MMP activity was increased during I/R by 122 +/- 10% (P 
      < 0.05) and was unchanged from baseline with ET antagonism and/or PKC inhibition. 
      Selective PKC isoform induction occurred such that PKC-betaII increased by 198 
      +/- 31% (P < 0.05). MT1-MMP phosphothreonine, a putative PKC phosphorylation 
      site, was increased by 121 +/- 8% (P < 0.05) in the I/R region. These studies 
      demonstrate for the first time that increased interstitial MT1-MMP activity 
      during I/R is a result of the ET/PKC pathway and may be due to enhanced 
      phosphorylation of MT1-MMP. These findings identify multiple potential targets 
      for modulating a local proteolytic pathway operative during I/R.
FAU - Deschamps, Anne M
AU  - Deschamps AM
AD  - Division of Cardiothoracic Surgery, Medical University of South Carolina, 
      Charleston, SC 29403, USA.
FAU - Zavadzkas, Juozas
AU  - Zavadzkas J
FAU - Murphy, Rebecca L
AU  - Murphy RL
FAU - Koval, Christine N
AU  - Koval CN
FAU - McLean, Julie E
AU  - McLean JE
FAU - Jeffords, Laura
AU  - Jeffords L
FAU - Saunders, Stuart M
AU  - Saunders SM
FAU - Sheats, Nina J
AU  - Sheats NJ
FAU - Stroud, Robert E
AU  - Stroud RE
FAU - Spinale, Francis G
AU  - Spinale FG
LA  - eng
GR  - HL-59165/HL/NHLBI NIH HHS/United States
GR  - R01 HL057952-09/HL/NHLBI NIH HHS/United States
GR  - R03 HL097012/HL/NHLBI NIH HHS/United States
GR  - HL-07260/HL/NHLBI NIH HHS/United States
GR  - R01 HL057952/HL/NHLBI NIH HHS/United States
GR  - R01 HL059165/HL/NHLBI NIH HHS/United States
GR  - P01 HL048788/HL/NHLBI NIH HHS/United States
GR  - P01-HL-48788/HL/NHLBI NIH HHS/United States
GR  - HL-45024/HL/NHLBI NIH HHS/United States
GR  - T32 HL007260/HL/NHLBI NIH HHS/United States
GR  - HL-97012/HL/NHLBI NIH HHS/United States
GR  - HL-57952/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20071207
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Endothelin B Receptor Antagonists)
RN  - 0 (Endothelins)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Isoenzymes)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Receptor, Endothelin B)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.24.80 (Matrix Metalloproteinase 14)
RN  - S2A8YZM151 (cyclo(Trp-Asp-Pro-Val-Leu))
SB  - IM
MH  - Animals
MH  - Endothelin B Receptor Antagonists
MH  - Endothelins/*physiology
MH  - Fluorescent Dyes
MH  - Immunoprecipitation
MH  - Isoenzymes/metabolism
MH  - Matrix Metalloproteinase 14/*metabolism
MH  - Microdialysis
MH  - Myocardial Reperfusion Injury/enzymology/*physiopathology
MH  - Peptides, Cyclic/pharmacology
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Receptor, Endothelin B/metabolism
MH  - Signal Transduction/*physiology
MH  - Stroke Volume/physiology
MH  - Swine
MH  - Threonine/metabolism
PMC - PMC2663358
MID - NIHMS97976
EDAT- 2007/12/11 09:00
MHDA- 2008/04/01 09:00
PMCR- 2009/03/31
CRDT- 2007/12/11 09:00
PHST- 2007/12/11 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/12/11 09:00 [entrez]
PHST- 2009/03/31 00:00 [pmc-release]
AID - 00918.2007 [pii]
AID - 10.1152/ajpheart.00918.2007 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H875-83. doi: 
      10.1152/ajpheart.00918.2007. Epub 2007 Dec 7.