Document Detail

Attenuation of increased secretory leukocyte protease inhibitor, matricellular proteins and angiotensin II and left ventricular remodeling by candesartan and omapatrilat during healing after reperfused myocardial infarction.
MedLine Citation:
PMID:  23361363     Owner:  NLM     Status:  MEDLINE    
While secretory-leukocyte-protease-inhibitor (SLPI) may promote skin wound healing, its role in infarct healing after reperfused myocardial infarction (RMI) remains unclear. Short-term intravenous angiotensin II (AngII) receptor blocker therapy with candesartan (CN) attenuates increased SLPI and markers of early matrix/left ventricular (LV) in acute RMI. To determine whether reducing effects of AngII with CN or the vasopeptidase inhibitor omapatrilat (OMA) during the healing phase after RMI attenuates SLPI and other mediators of healing and matrix/LV remodeling, we measured these in Sprague-Dawley rats randomized to oral placebo, CN (30 mg/kg/day) or OMA (10 mg/kg/day) therapy during healing between days 2 and 23 after RMI and sham. On day-25, RMI-placebo showed significant LV remodeling, systolic/diastolic dysfunction and impaired passive compliance, and ischemic zone increases in SLPI, secreted-protein-acidic-and-rich-in-cysteine (SPARC) and osteopontin (OPN) mRNA and protein. In addition, metalloproteinase (MMP)-9 and -2, a-disintegrin-and-metalloproteinase (ADAM)-10 and -17, inducible-nitric-oxide-synthase (iNOS), pro-inflammatory cytokines interleukin (IL)-6, and tumor necrosis factor-α, transforming growth factor (TGF)-β(1) and its signaling molecule p-Smad-2, myeloperoxidase (MPO), AngII, MPO-positive granulocytes, MAC387-positive macrophages and monocytes, scar collagens, cardiomyocyte and fibroblast apoptosis, and microvascular no-reflow also increased whereas anti-inflammatory cytokine IL-10 decreased. Both CN and OMA attenuated all the changes except IL-10, which normalized. Thus, CN or OMA treatment during healing after RMI results in attenuation of SLPI as well as tissue AngII and mediators of inflammation and matrix/LV remodeling including SPARC, OPN, and ADAMs. Whether increasing SLPI on top of background AngII inhibition or therapy such as CN or OMA might produce added remodeling benefit needs study.
Ariv Palaniyappan; Richard R E Uwiera; Halliday Idikio; Vijay Menon; Catherine Jugdutt; Bodh I Jugdutt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-30
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  376     ISSN:  1573-4919     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-10-17     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  175-88     Citation Subset:  IM    
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MeSH Terms
Angiotensin II / metabolism*
Angiotensin II Type 1 Receptor Blockers / pharmacology
Apoptosis / drug effects
Benzimidazoles / pharmacology*
Collagen / metabolism
Myocardial Infarction / drug therapy*,  metabolism,  mortality,  physiopathology
Myocardial Reperfusion
Osteonectin / metabolism
Pyridines / pharmacology*
Rats, Sprague-Dawley
Secretory Leukocyte Peptidase Inhibitor / metabolism*
Tetrazoles / pharmacology*
Thiazepines / pharmacology*
Ventricular Remodeling / drug effects*
Reg. No./Substance:
0/Angiotensin II Type 1 Receptor Blockers; 0/Benzimidazoles; 0/Osteonectin; 0/Pyridines; 0/Secretory Leukocyte Peptidase Inhibitor; 0/Slpi protein, rat; 0/Tetrazoles; 0/Thiazepines; 11128-99-7/Angiotensin II; 36NLI90E7T/omapatrilat; 9007-34-5/Collagen; S8Q36MD2XX/candesartan

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

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