Faculty Collaboration Database

Localized delivery of mechano-growth factor E-domain peptide via polymeric microstructures improves cardiac function following myocardial infarction. Biomaterials 2015 Apr;46:26-34

Date

02/14/2015

Pubmed ID

25678113

Pubmed Central ID

PMC4328136

DOI

10.1016/j.biomaterials.2014.12.050

Scopus ID

2-s2.0-84922778332 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

The Insulin like growth factor-I isoform mechano-growth factor (MGF), is expressed in the heart following myocardial infarction and encodes a unique E-domain region. To examine E-domain function, we delivered a synthetic peptide corresponding to the unique E-domain region of the human MGF (IGF-1Ec) via peptide eluting polymeric microstructures to the heart. The microstructures were made of poly (ethylene glycol) dimethacrylate hydrogel and bioengineered to be the same size as an adult cardiac myocyte (100 × 15 × 15 μm) and with a stiffness of 20 kPa. Peptide eluting microrods and empty microrods were delivered via intramuscular injection following coronary artery ligation in mice. To examine the physiologic consequences, we assessed the impact of peptide delivery on cardiac function and cardiovascular hemodynamics using pressure-volume loops and gene expression by quantitative RT-PCR. A significant decline in both systolic and diastolic function accompanied by pathologic hypertrophy occurred by 2 weeks which decompensated further by 10 weeks post-infarct in the untreated groups. Delivery of the E-domain peptide eluting microrods decreased mortality, ameliorated the decline in hemodynamics, and delayed decompensation. This was associated with the inhibition of pathologic hypertrophy despite increasing vascular impedance. Delivery of the empty microrods had limited effects on hemodynamics and while pathologic hypertrophy persisted there was a decrease in ventricular stiffness. Our data show that cardiac restricted administration of the MGF E-domain peptide using polymeric microstructures may be used to prevent adverse remodeling of the heart and improve function following myocardial infarction.

Author List

Peña JR, Pinney JR, Ayala P, Desai TA, Goldspink PH

MESH terms used to index this publication - Major topics in bold

Animals
Drug Delivery Systems
Gene Expression Regulation
Heart Function Tests
Humans
Insulin-Like Growth Factor I
Kaplan-Meier Estimate
Magnetic Resonance Spectroscopy
Male
Mice, Inbred C57BL
Myocardial Contraction
Myocardial Infarction
Organ Size
Peptides
Polymers
Protein Structure, Tertiary