Despite improvements in therapeutics, ischemic heart disease remains a leading cause
of death. Cardiac remodeling after myocardial infarction (MI), predominantly due to
loss of cardiomyocytes and coronary vasculature, leads to a progressive decline in
cardiac function resulting in heart failure. Current therapies for cardiac repair
and heart failure are of limited benefit. Cell transplantation therapy upon MI is
a very promising therapeutic strategy to replace dead myocardium, reducing scarring
and improving cardiac performance.
METHODS AND RESULTS
Our research focuses on endothelial colony-forming cell-derived exosomes (ECFC-exosomes),
which are actively secreted endocytic nanovesicles (30-100 nm) that transport functional
miRNAs, proteins, mRNAs, and lipids, playing a key role in paracrine intercellular
communication. We identified a novel ability of ECFC-exosomes to promote angiogenesis
and cardiac tissue repair. Administration of ECFCs to mice following experimental
end-organ ischemia resulted in ECFC-exosome-dependent increase in angiogenesis. ECFC-derived
exosomes were taken up by endothelial cells leading to their proliferation and migration,
tube formation, and formation of new vessels. Administration of ECFC-exosome to a
murine model of myocardial infarction prevented cardiac remodeling and heart failure.
Next generation sequencing and bioinformatics analyses identified 136 miRNAs present
in ECFC-exosome cargo, and factor inhibiting HIF-1α and PTEN as their potential targets
in endothelial cells.
Our findings support the view that the ECFC-exosomes represent a novel therapeutic
approach to improve cardiac repair after MI.