PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors

• Published in: PloS one Vol. 6; no. 9; p. e24872
• Main Authors: Iwasaki, Hiroto, Kawamoto, Atsuhiko, Tjwa, Marc, Horii, Miki, Hayashi, Saeko, Oyamada, Akira, Matsumoto, Tomoyuki, Suehiro, Shigefumi, Carmeliet, Peter, Asahara, Takayuki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-09-2011; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Animals; Apoptosis; Biology; Biomedical research; Bone growth; Bone marrow; Bone Marrow Cells - cytology; Cardiomyocytes; Cardiomyopathy; Cell Proliferation; Clinical trials; Coronary artery disease; Cytokines; Developmental biology; Electrocardiography - methods; Female; Gene therapy; Gene Transfer Techniques; Genes; Green Fluorescent Proteins - chemistry; Growth factors; Health aspects; Heart; Heart attack; Heart diseases; Heart surgery; Hemodynamics; Humans; Hypoxia; Insulin; Insulin-like growth factors; Ischemia; Kinases; Laboratory animals; Maintenance; Male; Medical research; Medical treatment; Medicine; Mice; Mice, Transgenic; Myocardial infarction; Myocardial ischemia; Myocardial Ischemia - metabolism; Myocardial Ischemia - therapy; Myocardium - pathology; Neovascularization, Pathologic; Nitric oxide; Paracrine signalling; Peripheral blood; Phenotype; Placenta; Placenta Growth Factor; Pregnancy Proteins - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Recruitment; Regeneration; Repair; Rodents; Smooth muscle; Stem cells; Stem Cells - cytology; Tissue engineering; Transcription factors; Transplants & implants; Vascular endothelial growth factor; Vascular endothelial growth factor receptors; Belgium; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024872

Despite preclinical success in regenerating and revascularizing the infarcted heart using angiogenic growth factors or bone marrow (BM) cells, recent clinical trials have revealed less benefit from these therapies than expected.
We explored the therapeutic potential of myocardial gene therapy of placental growth factor (PlGF), a VEGF-related angiogenic growth factor, with progenitor-mobilizing activity.
Myocardial PlGF gene therapy improves cardiac performance after myocardial infarction, by inducing cardiac repair and reparative myoangiogenesis, via upregulation of paracrine anti-apoptotic and angiogenic factors. In addition, PlGF therapy stimulated Sca-1(+)/Lin(-) (SL) BM progenitor proliferation, enhanced their mobilization into peripheral blood, and promoted their recruitment into the peri-infarct borders. Moreover, PlGF enhanced endothelial progenitor colony formation of BM-derived SL cells, and induced a phenotypic switch of BM-SL cells, recruited in the infarct, to the endothelial, smooth muscle and cardiomyocyte lineage.
Such pleiotropic effects of PlGF on cardiac repair and regeneration offer novel opportunities in the treatment of ischemic heart disease.