Treatment With Recombinant Placental Growth Factor (PlGF) Enhances Both Angiogenesis and Arteriogenesis and Improves Survival After Myocardial Infarction

Yukiji Takeda; Shiro Uemura; Hajime Iwama; Kei-ichi Imagawa; Taku Nishida; Kenji Onoue; Yasuhiro Takemoto; Tsunenari Soeda; Satoshi Okayama; Satoshi Somekawa; Ken-ichi Ishigami; Minoru Takaoka; Hiroyuki Kawata; Atsushi Kubo; Manabu Horii; Tamio Nakajima; Yoshihiko Saito

doi:10.1253/circj.CJ-08-1067

Ischemic Heart Disease

Treatment With Recombinant Placental Growth Factor (PlGF) Enhances Both Angiogenesis and Arteriogenesis and Improves Survival After Myocardial Infarction

Yukiji Takeda, Shiro Uemura, Hajime Iwama, Kei-ichi Imagawa, Taku Nishida, Kenji Onoue, Yasuhiro Takemoto, Tsunenari Soeda, Satoshi Okayama, Satoshi Somekawa, Ken-ichi Ishigami, Minoru Takaoka, Hiroyuki Kawata, Atsushi Kubo, Manabu Horii, Tamio Nakajima, Yoshihiko Saito

Author information

Yukiji Takeda
First Department of Internal Medicine, Nara Medical University
Shiro Uemura
First Department of Internal Medicine, Nara Medical University
Hajime Iwama
First Department of Internal Medicine, Nara Medical University
Kei-ichi Imagawa
First Department of Internal Medicine, Nara Medical University
Taku Nishida
First Department of Internal Medicine, Nara Medical University
Kenji Onoue
First Department of Internal Medicine, Nara Medical University
Yasuhiro Takemoto
First Department of Internal Medicine, Nara Medical University
Tsunenari Soeda
First Department of Internal Medicine, Nara Medical University
Satoshi Okayama
First Department of Internal Medicine, Nara Medical University
Satoshi Somekawa
First Department of Internal Medicine, Nara Medical University
Ken-ichi Ishigami
First Department of Internal Medicine, Nara Medical University
Minoru Takaoka
First Department of Internal Medicine, Nara Medical University
Hiroyuki Kawata
First Department of Internal Medicine, Nara Medical University
Atsushi Kubo
First Department of Internal Medicine, Nara Medical University
Manabu Horii
First Department of Internal Medicine, Nara Medical University
Tamio Nakajima
First Department of Internal Medicine, Nara Medical University
Yoshihiko Saito
First Department of Internal Medicine, Nara Medical University

Keywords: Myocardial infarction, Placental growth factor, Soluble Flt-1

JOURNAL FREE ACCESS

2009 Volume 73 Issue 9 Pages 1674-1682

DOI https://doi.org/10.1253/circj.CJ-08-1067

View "Advance Publication" version (July 15, 2009).

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Abstract

Background: Placental growth factor (PlGF), a homolog of vascular endothelial growth factor, is reported to stimulate angiogenesis and arteriogenesis in pathological conditions. It was recently demonstrated that PlGF is rapidly produced in myocardial tissue during acute myocardial infarction (MI). However, the effects of exogenous PlGF administration on the healing process after MI are not fully understood. The purpose of the present study was to examine whether PlGF treatment has therapeutic potential in MI. Methods and Results: Recombinant human PlGF (rhPlGF: 10 μg) was administered continuously for 3 days in a mouse model of acute MI. rhPlGF treatment significantly improved survival rate after MI and preserved cardiac function relative to control mice. The numbers of CD31-positive cells and α-smooth muscle actin-positive vessels in the infarct area were significantly increased in the rhPlGF group. Endothelial progenitor cells (Flk-1⁺Sca-1⁺ cells) were mobilized by rhPlGF into the peripheral circulation. Furthermore, rhPlGF promoted the recruitment of GFP-labeled bone marrow cells to the infarct area, but only a few of those migrating cells differentiated into endothelial cells. Conclusions: Exogenous PlGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following MI. It can be considered as a new therapeutic molecule. (Circ J 2009; 73: 1674-1682)

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