Document Detail

Targeted Injection of a Biocomposite Material Alters Macrophage and Fibroblast Phenotype and Function Following Myocardial Infarction: Relation to LV Remodeling.
MedLine Citation:
PMID:  25022514     Owner:  NLM     Status:  Publisher    
A treatment target for progressive LV remodeling prevention following myocardial infarction (MI) is to affect structural changes directly within the MI region. One approach is through targeted injection of biocomposite materials, such as calcium hydroxyapatite (CHAM), into the MI region. In this study, the effects of CHAM injections upon key cell types responsible for the MI remodeling process, the macrophage (MAC) and fibroblast (FIBRO), were examined. MI was induced in adult pigs before randomization to CHAM injections (20, 0.1mL, targeted injections within MI region) or saline. At 7 or 21 days post-MI (n=6/time point/group), cardiac MRI was performed, followed by MAC and FIBRO isolation. Isolated MAC profiles for monocyte chemotactic MAC inflammatory protein-1 (MCP-1) as measured by rtPCR increased at 7 days post-MI in the CHAM group compared to MI only (16.3+6.6 vs 1.7+0.6 Ct values, p<0.05) and were similar by 21 days post-MI. Temporal changes in FIBRO function and smooth muscle actin (SMA) expression relative to referent control (n=5) occurred with MI. CHAM induced increases in FIBRO proliferation, migration, and SMA expression - indicative of FIBRO transformation. By 21 days, CHAM reduced LV dilation (diastolic volume: 75+2 vs 97+4 mL) and increased function (ejection fraction: 48+2 vs 38+2 %) compared to MI only (both p<0.05). This study identified that effects on macrophage and fibroblast differentiation occurred with injection of biocomposite material within the MI, which translated into reduced adverse LV remodeling. These unique findings demonstrate biomaterial injections impart biological effects upon the MI remodeling process over any biophysical effects.
Jeremy R McGarvey; Sara Pettaway; James Shuman; Craig P Novack; Kia N Zellars; Parker Freels; Randall L Echols; Jason A Burdick; Joseph H Gorman; Robert C Gorman; Francis G Spinale
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-14
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  -     ISSN:  1521-0103     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
The American Society for Pharmacology and Experimental Therapeutics.
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