Document Detail


Targeted regional injection of biocomposite microspheres alters post-myocardial infarction remodeling and matrix proteolytic pathways.
MedLine Citation:
PMID:  21911817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jennifer A Dixon; Robert C Gorman; Robert E Stroud; Rupak Mukherjee; Evan C Meyer; Nathaniel L Baker; Masato Morita; Hirotsugu Hamamoto; Liam P Ryan; Joseph H Gorman; Francis G Spinale
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  124     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-09-13     Completed Date:  2011-11-03     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S35-45     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Collagen / metabolism
Durapatite / administration & dosage,  pharmacology,  therapeutic use*
Extracellular Matrix / metabolism*
Injections
Male
Matrix Metalloproteinase 13 / metabolism
Matrix Metalloproteinases / metabolism*
Microspheres*
Models, Animal
Myocardial Infarction / drug therapy*,  metabolism,  physiopathology*
Sheep
Signal Transduction / drug effects,  physiology
Tissue Inhibitor of Metalloproteinases / metabolism*
Treatment Outcome
Ventricular Remodeling / drug effects*,  physiology
Grant Support
ID/Acronym/Agency:
HL57952/HL/NHLBI NIH HHS; HL59165/HL/NHLBI NIH HHS; HL63954/HL/NHLBI NIH HHS; HL73021/HL/NHLBI NIH HHS; HL78825/HL/NHLBI NIH HHS; HL95608/HL/NHLBI NIH HHS; R01 HL057952/HL/NHLBI NIH HHS; R01 HL057952-12/HL/NHLBI NIH HHS; R01 HL059165/HL/NHLBI NIH HHS; R01 HL059165-12/HL/NHLBI NIH HHS; R01 HL063954/HL/NHLBI NIH HHS; R01 HL063954-12/HL/NHLBI NIH HHS; R01 HL073021/HL/NHLBI NIH HHS; R01 HL073021-08/HL/NHLBI NIH HHS; R01 HL095608/HL/NHLBI NIH HHS; R01 HL095608-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Tissue Inhibitor of Metalloproteinases; 9007-34-5/Collagen; 91D9GV0Z28/Durapatite; EC 3.4.24.-/Matrix Metalloproteinase 13; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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