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Collagen-binding VEGF targeting the cardiac extracellular matrix promotes recovery in porcine chronic myocardial infarction.

Abstract
An effective therapy for chronic myocardial infarction (MI) has yet to be developed. Vascular endothelial growth factor (VEGF) promotes angiogenesis and improves cardiac function after MI. However, non-targeted delivery of VEGF decreases its therapeutic efficacy. In this study, for targeting the cardiac extracellular matrix, a collagen-binding domain (CBD) VEGF was used to bind specifically to the collagen-rich cardiac extracellular matrix. When intramyocardially injected into the peri-infarct region of a chronically infarcted porcine heart, CBD-VEGF attenuated the remodeling of the left ventricle with a decreased infarct size and promoted cardiomyocyte survival and angiogenesis 3 months after injection. In the 12-month trial, mature vessel networks and myocardium-like tissues were observed in the infarct region after CBD-VEGF injection. Also these beneficial effects might derive from CBD-VEGF significantly protecting cardiomyocytes from apoptosis and recruiting cardiac progenitor cells to the infarcted region. These results demonstrated that CBD-VEGF could be a promising therapeutic strategy for chronic MI.
AuthorsChunying Shi , Yannan Zhao , Yun Yang , Cheng Chen , Xianglin Hou , Jun Shao , Hao Yao , Qingguo Li , Yujun Xia , Jianwu Dai
JournalBiomaterials science (Biomater Sci) Vol. 6 Issue 2 Pg. 356-363 (Jan 30 2018) ISSN: 2047-4849 [Electronic] England
PMID29266144 (Publication Type: Journal Article)
Chemical References
  • Peptide Fragments
  • Vascular Endothelial Growth Factor A
  • Collagen
Topics
  • Animals
  • Apoptosis
  • Binding Sites
  • Collagen (metabolism)
  • Extracellular Matrix (metabolism)
  • Heart Ventricles (drug effects, pathology)
  • Injections, Intralesional
  • Male
  • Myocardial Infarction (drug therapy)
  • Myocytes, Cardiac (drug effects, metabolism)
  • Neovascularization, Physiologic
  • Peptide Fragments (administration & dosage, pharmacology, therapeutic use)
  • Protein Binding
  • Swine
  • Vascular Endothelial Growth Factor A (chemistry)

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