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Nebulized delivery of the MAPKAP kinase 2 peptide inhibitor MMI‐0100 protects against ischemia‐induced systolic dysfunction
Author(s) -
Brown David,
Cooley Brian,
Quintana Megan,
Landers Cynthia,
Willis Monte S
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.306.3
Subject(s) - medicine , ligation , fibrosis , myocardial infarction , cardiology , cardiac fibrosis , inflammation , myocarditis , myocardial fibrosis
Acute myocardial infarction (AMI) results in systolic dysfunction, myocarditis and fibrotic remodeling, which causes irreversible pathological remodeling of the heart. Associated cell death and inflammation cause cytokine release, which activates the p38 MAPK signaling pathway to propagate damaging signals via MAPKAP kinase 2 (MK2). Previously we showed that intraperitoneal injection of a cell permeable peptide inhibitor of MK2, MMI‐0100, protects against fibrosis, apoptosis and systolic dysfunction in a mouse model of AMI, left‐anterior descending coronary artery (LAD) ligation. Here we tested a new route of administration of MMI‐0100: inhalation of nebulized peptide. When given within 30 minutes of AMI and daily for 2 weeks thereafter, both inhaled and injected MMI‐0100 improved cardiac function as measured by conscious echocardiography. Limited fibrosis was observed after two weeks by Massons trichrome staining, suggesting that MMI‐0100 protects the heart prior to the formation of significant fibrosis. These results support a nebulized route of administration of MMI‐0100 can protect the myocardium from ischemic damage. Support or Funding Information This work was supported by the National Institutes of Health (R01HL104129 to M.W.), a Fellowship from the Jefferson‐Pilot Corporation (to M.W.), and the Leducq Foundation (to M.W.).