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VEGF-B Promotes End...
VEGF-B Promotes Endocardium-Derived Coronary Vessel Development and Cardiac Regeneration
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- Räsänen, Markus (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Sultan, Ibrahim (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Paech, Jennifer (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Hemanthakumar, Karthik Amudhala (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Yu, Wei (author)
- Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem, Beijing, Peoples R China
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- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi,Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin Neurol Inst,Minist Educ & Tianjin City, Key Lab Postneuroinjury Neurorepair & Regenerat C, Tianjin, Peoples R China
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- Tang, Juan (author)
- Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem, Beijing, Peoples R China
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- Sun, Ying (author)
- Uppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab
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- Hlushchuk, Ruslan (author)
- Univ Bern, Inst Anat, Bern, Switzerland
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- Huan, Xiuzheng (author)
- Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem, Beijing, Peoples R China
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- Armstrong, Emma (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland; Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Khoma, Oleksiy-Zakhar (author)
- Univ Bern, Inst Anat, Bern, Switzerland
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- Mervaala, Eero (author)
- Univ Helsinki, Fac Med, Helsinki, Finland
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- Djonov, Valentin (author)
- Univ Bern, Inst Anat, Bern, Switzerland
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Integrated Cardio Metab Ctr, Huddinge, Sweden
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- Zhou, Bin (author)
- Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci,Shanghai Inst Biochem, Beijing, Peoples R China
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- Kivelä, Riikka (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland.;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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- Alitalo, Kari (author)
- Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland; Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland
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Univ Helsinki, Fac Med, Wihuri Res Inst, Helsinki, Finland;Univ Helsinki, Fac Med, Translat Canc Med Program, Helsinki, Finland Univ Chinese Acad Sci, Chinese Acad Sci, State Key Lab Cell Biol, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem, Beijing, Peoples R China (creator_code:org_t)
- Wolters Kluwer, 2021
- 2021
- English.
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In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 143:1, s. 65-77
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Abstract
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- Background:Recent discoveries have indicated that, in the developing heart, sinus venosus and endocardium provide major sources of endothelium for coronary vessel growth that supports the expanding myocardium. Here we set out to study the origin of the coronary vessels that develop in response to vascular endothelial growth factor B (VEGF-B) in the heart and the effect of VEGF-B on recovery from myocardial infarction.Methods:We used mice and rats expressing a VEGF-B transgene, VEGF-B-gene–deleted mice and rats, apelin-CreERT, and natriuretic peptide receptor 3–CreERT recombinase-mediated genetic cell lineage tracing and viral vector–mediated VEGF-B gene transfer in adult mice. Left anterior descending coronary vessel ligation was performed, and 5-ethynyl-2’-deoxyuridine–mediated proliferating cell cycle labeling; flow cytometry; histological, immunohistochemical, and biochemical methods; single-cell RNA sequencing and subsequent bioinformatic analysis; microcomputed tomography; and fluorescent- and tracer-mediated vascular perfusion imaging analyses were used to study the development and function of the VEGF-B–induced vessels in the heart.Results:We show that cardiomyocyte overexpression of VEGF-B in mice and rats during development promotes the growth of novel vessels that originate directly from the cardiac ventricles and maintain connection with the coronary vessels in subendocardial myocardium. In adult mice, endothelial proliferation induced by VEGF-B gene transfer was located predominantly in the subendocardial coronary vessels. Furthermore, VEGF-B gene transduction before or concomitantly with ligation of the left anterior descending coronary artery promoted endocardium-derived vessel development into the myocardium and improved cardiac tissue remodeling and cardiac function.Conclusions:The myocardial VEGF-B transgene promotes the formation of endocardium-derived coronary vessels during development, endothelial proliferation in subendocardial myocardium in adult mice, and structural and functional rescue of cardiac tissue after myocardial infarction. VEGF-B could provide a new therapeutic strategy for cardiac neovascularization after coronary occlusion to rescue the most vulnerable myocardial tissue.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- cardiac protection
- gene therapy
- myocardial ischemia
- revascularization
- VEGF
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Räsänen, Markus
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Sultan, Ibrahim
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Paech, Jennifer
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Hemanthakumar, K ...
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Yu, Wei
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He, Liqun
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show more...
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Tang, Juan
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Sun, Ying
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Hlushchuk, Rusla ...
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Huan, Xiuzheng
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Armstrong, Emma
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Khoma, Oleksiy-Z ...
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Mervaala, Eero
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Djonov, Valentin
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Betsholtz, Chris ...
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Zhou, Bin
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Kivelä, Riikka
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Alitalo, Kari
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Circulation
- By the university
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Uppsala University
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Karolinska Institutet