Journal article
Cardiac Progenitor Cell Recruitment Drives Fetal Cardiac Regeneration by Enhanced Angiogenesis
The Annals of thoracic surgery, v 104(6), pp 1968-1975
Dec 2017
PMID: 28821329
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In contrast to adults, the fetal response to myocardial infarction (MI) is regenerative, requiring the recruitment of cardiac progenitor cells to replace infarcted myocardium. Macrophage contribution to tissue repair depends on their phenotype: M1 are proinflammatory and initiate angiogenesis; M2a are profibrotic and contribute to blood vessels maturation; and M2c are proremodeling and proangiogenesis. The goal of the present study was to expand on this work by examining cardiac progenitor cells recruitment, and the role of macrophages in promoting angiogenesis and cardiac regeneration in the fetal heart after MI.
Fetal and adult sheep underwent MI and were sacrificed 3 or 30 days after MI. Some fetal hearts received stromal cell-derived factor-1α-inhibitor treatment. The microvasculature was evaluated by micro-computed tomography, gene expression was evaluated by real-time polymerase chain reaction, and vessels counts were evaluated by immunohistochemistry.
Micro-computed tomography analysis showed restoration of microvasculature in fetal hearts after MI. Vascular endothelial growth factor-α increased, and the expression of tissue markers associated with the M1, M2a, and M2c macrophage phenotypes were elevated at day 3 after MI, but returned to baseline by 30 days after MI. In contrast, adult hearts after MI exhibited low vascular endothelial growth factor-α and persistent upregulation of all macrophage markers, consistent with prolonged inflammation, fibrosis, and remodeling. Inhibition of stromal cell-derived factor-1α in fetal infarcts prevented angiogenesis, decreased vascular endothelial growth factor-α, and was associated with a sustained increase in M1, M2a, and M2c markers after MI.
Changes in angiogenesis and macrophage phenotype-related gene expression after MI are important for the fetal regenerative response to MI and are mediated at least in part by cardiac progenitor cells recruitment.
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Details
- Title
- Cardiac Progenitor Cell Recruitment Drives Fetal Cardiac Regeneration by Enhanced Angiogenesis
- Creators
- Carlos Zgheib - Children's Hospital ColoradoMaggie M Hodges - Children's Hospital ColoradoMyron W Allukian - University of PennsylvaniaJunwang Xu - Children's Hospital ColoradoKara L Spiller - Drexel UniversityJoseph H Gorman, 3rd - Department of Surgery and Gorman Cardiovascular Research Group, University of Pennsylvania School of Medicine, Philadelphia, PennsylvaniaRobert C Gorman - University of PennsylvaniaKenneth W Liechty - Laboratory for Fetal and Regenerative Biology, Department of Surgery, School of Medicine, University of Colorado Denver, Anschutz Medical Campus and Colorado Children's Hospital, Aurora, Colorado. Electronic address: kenneth.liechty@childrenscolorado.org
- Publication Details
- The Annals of thoracic surgery, v 104(6), pp 1968-1975
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000415802000047
- Scopus ID
- 2-s2.0-85027462667
- Other Identifier
- 991019168163704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Respiratory System
- Surgery