Abstract | BACKGROUND: METHODS: AMI was induced by permanent ligation of the left coronary artery. Adult, male, Imprinting Control Region mice were randomized to daily injections with 1 of 2 MyD88 pharmacologic inhibitors ( ST2825 25 mg/kg or IMG2005 1 mg/kg), saline, or pretreatment with MyD88-targeted silencing small interfering RNA ( siRNA) or scrambled nontargeted siRNA (n = 6 for each group). Echocardiography was performed at baseline and 7 days after surgery to evaluate pathologic cardiac enlargement. RESULTS: Pharmacologic inhibition of MyD88 with ST2825 or IMG2005) and MyD88-targeted siRNA protected against left ventricular (LV) dilatation (reduced LV end-systolic and LV end-diastolic diameter) and hypertrophy. This protection occurred despite no measurable reduction in infarct size. CONCLUSIONS: Pharmacologic MyD88 inhibition protects against pathologic LV remodeling without altering infarct scar formation. MyD88 may be a viable target for pharmacologic inhibition in AMI.
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Authors | Benjamin W Van Tassell, Ignacio M Seropian, Stefano Toldo, Fadi N Salloum, Lisa Smithson, Amit Varma, Nicholas N Hoke, Christopher Gelwix, Vinh Chau, Antonio Abbate |
Journal | Journal of cardiovascular pharmacology
(J Cardiovasc Pharmacol)
Vol. 55
Issue 4
Pg. 385-90
(Apr 2010)
ISSN: 1533-4023 [Electronic] United States |
PMID | 20125030
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Heterocyclic Compounds, 2-Ring
- Interleukin-1beta
- Interleukin-6
- Myd88 protein, mouse
- Myeloid Differentiation Factor 88
- NF-kappa B
- RNA, Small Interfering
- ST2825
- Spiro Compounds
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Topics |
- Animals
- Heart
(drug effects)
- Heart Ventricles
(drug effects, pathology)
- Heterocyclic Compounds, 2-Ring
(pharmacology, therapeutic use)
- Hypertrophy, Left Ventricular
(pathology, prevention & control)
- Interleukin-1beta
(pharmacology)
- Interleukin-6
(blood)
- Male
- Mice
- Mice, Inbred ICR
- Myeloid Differentiation Factor 88
(antagonists & inhibitors, genetics, metabolism)
- Myocardial Infarction
(drug therapy, pathology, therapy)
- Myocardium
(metabolism, pathology)
- NF-kappa B
(metabolism)
- RNA, Small Interfering
(administration & dosage, genetics, therapeutic use)
- Spiro Compounds
(pharmacology, therapeutic use)
- Ventricular Remodeling
(drug effects)
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