PMID- 21911817
OWN - NLM
STAT- MEDLINE
DCOM- 20111103
LR  - 20211020
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 124
IP  - 11 Suppl
DP  - 2011 Sep 13
TI  - Targeted regional injection of biocomposite microspheres alters post-myocardial 
      infarction remodeling and matrix proteolytic pathways.
PG  - S35-45
LID - 10.1161/CIRCULATIONAHA.111.035774 [doi]
AB  - BACKGROUND: Although localized delivery of biocomposite materials, such as 
      calcium hydroxyapatite (CHAM), have been demonstrated to potentially attenuate 
      adverse left ventricular (LV) remodeling after myocardial infarction (MI), the 
      underlying biological mechanisms for this effect remain unclear. This study 
      tested the hypothesis that targeted CHAM injections would alter proteolytic 
      pathways (matrix metalloproteinases [MMPs] and tissue inhibitors of MMPs [TIMPs]) 
      and would be associated with parameters of post-MI LV remodeling. METHODS AND 
      RESULTS: MI was induced in adult sheep followed by 20 targeted injections of a 
      total volume of 1.3 mL (n=6) or 2.6 mL of CHAM (n=5) or saline (n=13) and LV 
      end-diastolic volume (EDV) and MMP/TIMP profiles in the MI region were measured 
      at 8 weeks after MI. LV EDV decreased with 2.6 mL CHAM versus MI only (105.4 +/- 
      7.5 versus 80.6 +/- 4.2 respectively, P<0.05) but not with 1.3 mL CHAM (94.5 +/- 5.0, 
      P=0.32). However, MI thickness increased by 2-fold in both CHAM groups compared 
      with MI only (P<0.05). MMP-13 increased 40-fold in the MI only group (P<0.05) but 
      fell by >6-fold in both CHAM groups (P<0.05). MMP-7 increased approximately 
      1.5-fold in the MI only group (P<0.05) but decreased to referent control values 
      in both CHAM groups in the MI region (P<0.05). Collagen content was reduced by 
      approximately 30% in the CHAM groups compared with MI only (P<0.05). CONCLUSIONS: 
      Differential effects on LV remodeling and MMP/TIMP profiles occurred with CHAM. 
      Thus, targeted injection of a biocomposite material can favorably affect the 
      post-MI remodeling process and therefore holds promise as a treatment strategy in 
      and of itself, or as a matrix with potentially synergistic effects with localized 
      pharmacological or cellular therapies.
FAU - Dixon, Jennifer A
AU  - Dixon JA
AD  - Cardiothoracic Surgery, Medical University of SouthCarolina and Ralph H. Johnson 
      Veterans Affairs Medical Center, Charleston, SC, USA.
FAU - Gorman, Robert C
AU  - Gorman RC
FAU - Stroud, Robert E
AU  - Stroud RE
FAU - Mukherjee, Rupak
AU  - Mukherjee R
FAU - Meyer, Evan C
AU  - Meyer EC
FAU - Baker, Nathaniel L
AU  - Baker NL
FAU - Morita, Masato
AU  - Morita M
FAU - Hamamoto, Hirotsugu
AU  - Hamamoto H
FAU - Ryan, Liam P
AU  - Ryan LP
FAU - Gorman, Joseph H 3rd
AU  - Gorman JH 3rd
FAU - Spinale, Francis G
AU  - Spinale FG
LA  - eng
GR  - HL78825/HL/NHLBI NIH HHS/United States
GR  - HL63954/HL/NHLBI NIH HHS/United States
GR  - R01 HL073021/HL/NHLBI NIH HHS/United States
GR  - R01 HL057952/HL/NHLBI NIH HHS/United States
GR  - R01 HL059165-12/HL/NHLBI NIH HHS/United States
GR  - R01 HL095608/HL/NHLBI NIH HHS/United States
GR  - P01 HL078825/HL/NHLBI NIH HHS/United States
GR  - HL73021/HL/NHLBI NIH HHS/United States
GR  - R01 HL059165/HL/NHLBI NIH HHS/United States
GR  - HL59165/HL/NHLBI NIH HHS/United States
GR  - R01 HL063954/HL/NHLBI NIH HHS/United States
GR  - R01 HL063954-12/HL/NHLBI NIH HHS/United States
GR  - HL57952/HL/NHLBI NIH HHS/United States
GR  - HL95608/HL/NHLBI NIH HHS/United States
GR  - R01 HL095608-03/HL/NHLBI NIH HHS/United States
GR  - R01 HL073021-08/HL/NHLBI NIH HHS/United States
GR  - R01 HL057952-12/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  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 9007-34-5 (Collagen)
RN  - 91D9GV0Z28 (Durapatite)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Collagen/metabolism
MH  - Durapatite/administration & dosage/pharmacology/*therapeutic use
MH  - Extracellular Matrix/*metabolism
MH  - Injections
MH  - Male
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - *Microspheres
MH  - Models, Animal
MH  - Myocardial Infarction/*drug therapy/metabolism/*physiopathology
MH  - Sheep
MH  - Signal Transduction/drug effects/physiology
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
MH  - Treatment Outcome
MH  - Ventricular Remodeling/*drug effects/physiology
PMC - PMC3218562
MID - NIHMS318382
EDAT- 2011/09/23 06:00
MHDA- 2011/11/04 06:00
PMCR- 2012/09/13
CRDT- 2011/09/14 06:00
PHST- 2011/09/14 06:00 [entrez]
PHST- 2011/09/23 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2012/09/13 00:00 [pmc-release]
AID - 124/11_suppl_1/S35 [pii]
AID - 10.1161/CIRCULATIONAHA.111.035774 [doi]
PST - ppublish
SO  - Circulation. 2011 Sep 13;124(11 Suppl):S35-45. doi: 
      10.1161/CIRCULATIONAHA.111.035774.