Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction

David I. Brown, Brian C. Cooley, Megan T. Quintana, Cynthia Lander, Monte Willis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 induced by 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 min 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 2 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.

Original languageEnglish (US)
Pages (from-to)317-324
Number of pages8
JournalInternational Journal of Peptide Research and Therapeutics
Volume22
Issue number3
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

Cell death
Peptides
Ischemia
Echocardiography
Fibrosis
Myocardial Infarction
Myocarditis
p38 Mitogen-Activated Protein Kinases
Intraperitoneal Injections
Inhalation
Ligation
Coronary Vessels
Myocardium
Cell Death
MMI-0100
MAP-kinase-activated kinase 2
Apoptosis
Staining and Labeling
Cytokines
Inflammation

Keywords

  • MAPKAP kinase 2
  • MK2
  • MK2 inhibitor
  • MMI-0100
  • Myocardial infarction
  • P38 MAPK
  • Peptide inhibitor

ASJC Scopus subject areas

  • Analytical Chemistry
  • Bioengineering
  • Biochemistry
  • Molecular Medicine
  • Drug Discovery

Cite this

Nebulized Delivery of the MAPKAP Kinase 2 Peptide Inhibitor MMI-0100 Protects Against Ischemia-Induced Systolic Dysfunction. / Brown, David I.; Cooley, Brian C.; Quintana, Megan T.; Lander, Cynthia; Willis, Monte.

In: International Journal of Peptide Research and Therapeutics, Vol. 22, No. 3, 01.09.2016, p. 317-324.

Research output: Contribution to journalArticle

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