PMID- 24523321
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20211021
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 6
IP  - 223
DP  - 2014 Feb 12
TI  - Local hydrogel release of recombinant TIMP-3 attenuates adverse left ventricular 
      remodeling after experimental myocardial infarction.
PG  - 223ra21
LID - 10.1126/scitranslmed.3007244 [doi]
AB  - An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of 
      MMPs (TIMPs) contributes to the left ventricle (LV) remodeling that occurs after 
      myocardial infarction (MI). However, translation of these observations into a 
      clinically relevant, therapeutic strategy remains to be established. The present 
      study investigated targeted TIMP augmentation through regional injection of a 
      degradable hyaluronic acid hydrogel containing recombinant TIMP-3 (rTIMP-3) in a 
      large animal model. MI was induced in pigs by coronary ligation. Animals were 
      then randomized to receive targeted hydrogel/rTIMP-3, hydrogel alone, or saline 
      injection and followed for 14 days. Instrumented pigs with no MI induction served 
      as referent controls. Multimodal imaging (fluoroscopy/echocardiography/magnetic 
      resonance imaging) revealed that LV ejection fraction was improved, LV dilation 
      was reduced, and MI expansion was attenuated in the animals treated with rTIMP-3 
      compared to all other controls. A marked reduction in proinflammatory cytokines 
      and increased smooth muscle actin content indicative of myofibroblast 
      proliferation occurred in the MI region with hydrogel/rTIMP-3 injections. These 
      results provide the first proof of concept that regional sustained delivery of an 
      MMP inhibitor can effectively interrupt adverse post-MI remodeling.
FAU - Eckhouse, Shaina R
AU  - Eckhouse SR
AD  - Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 
      29425, USA.
FAU - Purcell, Brendan P
AU  - Purcell BP
FAU - McGarvey, Jeremy R
AU  - McGarvey JR
FAU - Lobb, David
AU  - Lobb D
FAU - Logdon, Christina B
AU  - Logdon CB
FAU - Doviak, Heather
AU  - Doviak H
FAU - O'Neill, Jason W
AU  - O'Neill JW
FAU - Shuman, James A
AU  - Shuman JA
FAU - Novack, Craig P
AU  - Novack CP
FAU - Zellars, Kia N
AU  - Zellars KN
FAU - Pettaway, Sara
AU  - Pettaway S
FAU - Black, Roy A
AU  - Black RA
FAU - Khakoo, Aarif
AU  - Khakoo A
FAU - Lee, Taeweon
AU  - Lee T
FAU - Mukherjee, Rupak
AU  - Mukherjee R
FAU - Gorman, Joseph H
AU  - Gorman JH
FAU - Gorman, Robert C
AU  - Gorman RC
FAU - Burdick, Jason A
AU  - Burdick JA
FAU - Spinale, Francis G
AU  - Spinale FG
LA  - eng
GR  - R01 HL111090/HL/NHLBI NIH HHS/United States
GR  - T32 HL007954/HL/NHLBI NIH HHS/United States
GR  - T32HL007954/HL/NHLBI NIH HHS/United States
GR  - R01 HL057952/HL/NHLBI NIH HHS/United States
GR  - R01 HL095608/HL/NHLBI NIH HHS/United States
GR  - R01 HL059165/HL/NHLBI NIH HHS/United States
GR  - I01 BX000168/BX/BLRD VA/United States
GR  - HL095608/HL/NHLBI NIH HHS/United States
GR  - T32HL007260/HL/NHLBI NIH HHS/United States
GR  - HL057952/HL/NHLBI NIH HHS/United States
GR  - HL059165/HL/NHLBI NIH HHS/United States
GR  - T32 HL007260/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.
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Tissue Inhibitor of Metalloproteinase-3)
RN  - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Hydrogel, Polyethylene Glycol Dimethacrylate/administration & dosage/*chemistry
MH  - Myocardial Infarction/*drug therapy/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-3/*administration & 
      dosage/metabolism/*therapeutic use
MH  - Ventricular Remodeling/drug effects/*physiology
PMC - PMC4365799
MID - NIHMS669509
EDAT- 2014/02/14 06:00
MHDA- 2014/12/15 06:00
PMCR- 2015/03/19
CRDT- 2014/02/14 06:00
PHST- 2014/02/14 06:00 [entrez]
PHST- 2014/02/14 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2015/03/19 00:00 [pmc-release]
AID - 6/223/223ra21 [pii]
AID - 10.1126/scitranslmed.3007244 [doi]
PST - ppublish
SO  - Sci Transl Med. 2014 Feb 12;6(223):223ra21. doi: 10.1126/scitranslmed.3007244.