Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction.
Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Hai-dong
HD
Guo
Guo-hong
GH
Cui
Jia-jun
JJ
Yang
Cun
C
Wang
Jing
J
Zhu
Li-sheng
LS
Zhang
Jun
J
Jiang
Shui-jin
SJ
Shao
D000595:Amino Acid Sequence; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D040761:Biomimetic Materials / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D015195:Drug Design; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000187:drug effects*; D006493:Heparin / Q000737:chemistry; D018625:Microscopy, Atomic Force; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000737:chemistry; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000503:physiopathology*
D043925:Angiogenesis Inducing Agents; D003692:Delayed-Action Preparations; D042461:Vascular Endothelial Growth Factor A; D006493:Heparin