Cardiac-specific overexpression of human stem cell factor promotes epicardial activation and arteriogenesis after myocardial infarction.

Abstract

BACKGROUND:

The adult epicardium is a potential source of cardiac progenitors after myocardial infarction (MI). We tested the hypothesis that cardiomyocyte-specific overexpression of membrane-associated human stem cell factor (hSCF) enhances epicardial activation, epicardium-derived cells (EPDCs) production, and myocardial arteriogenesis post MI.

METHODS AND RESULTS:

Wild-type and the inducible cardiac-specific hSCF transgenic (hSCF/tetracycline transactivator) mice were subjected to MI. Wilms tumor-1 (Wt1)-positive epicardial cells were higher in hSCF/tetracycline transactivator compared with wild-type mice 3 days post MI. Arteriole density was significantly higher in the peri-infarct area of hSCF/tetracycline transactivator mice compared with wild-type mice 5 days post MI. In cultured EPDCs, adenoviral hSCF treatment significantly increased cell proliferation and growth factor expression. Furthermore, adenoviral hSCF treatment in wild-type cardiomyocytes significantly increased EPDC migration. These effects of hSCF overexpression on EPDC proliferation and growth factor expression were all abrogated by ACK2, a neutralizing antibody against c-kit. Finally, lineage tracing using ROSA(mTmG);Wt1(CreER) mice showed that adenoviral hSCF treatment increased Wt1(+) lineage-derived EPDC migration into the infarcted myocardium 5 days post MI, which was inhibited by ACK2.

CONCLUSIONS:

Cardiomyocyte-specific overexpression of hSCF promotes epicardial activation and myocardial arteriogenesis post MI.

• Authors: Fu-Li Xiang, Yin Liu, Xiangru Lu, Douglas L Jones, Qingping Feng
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 7 Issue 5 Pg. 831-42 (Sep 2014) ISSN: 1941-3297 [Electronic] United States
• PMID: 25107671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 American Heart Association, Inc.

Chemical References

• RNA, Messenger
• Stem Cell Factor

Topics

• Animals
• Animals, Newborn
• Blotting, Western
• Cell Proliferation
• Cells, Cultured
• Coronary Vessels (metabolism, pathology)
• Disease Models, Animal
• Gene Expression Regulation, Developmental
• Humans
• Immunohistochemistry
• Mice
• Mice, Transgenic
• Myocardial Infarction (genetics, metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Neovascularization, Pathologic
• Pericardium (metabolism, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Stem Cell Factor (biosynthesis, genetics)