CLINICAL RESEARCH
Cardiac Expression of Placental Growth Factor Predicts the Improvement of Chronic Phase Left Ventricular Function in Patients With Acute Myocardial Infarction
Hajime Iwama, MD,
Shiro Uemura, MD*,
Noriyuki Naya, BS,
Kei-ichi Imagawa, PhD,
Yasuhiro Takemoto, MD,
Osamu Asai, MD,
Kenji Onoue, MD,
Satoshi Okayama, MD,
Satoshi Somekawa, MD,
Yoshitomi Kida, MD,
Yukiji Takeda, MD,
Kimihiko Nakatani, MD,
Minoru Takaoka, MD,
Hiroyuki Kawata, MD,
Manabu Horii, MD,
Tamio Nakajima, MD,
Naofumi Doi, MD and
Yoshihiko Saito, MD
First Department of Medicine, Nara Medical University, Kashihara, Nara, Japan
Manuscript received December 17, 2004;
revised manuscript received October 26, 2005,
accepted November 8, 2005.
* Reprint requests and correspondence: Dr. Shiro Uemura, 840 Shijo-cho, Kashihara, Nara, Japan 634-8522 (Email: suemura{at}naramed-u.ac.jp).
OBJECTIVES: Our aim was to investigate cardiac expression of placental growth factor (PlGF) and its clinical significance in patients with acute myocardial infarction (AMI).
BACKGROUND: Placental growth factor is known to stimulate wound healing by activating mononuclear cells and inducing angiogenesis. The clinical significance of PlGF in AMI is not yet known.
METHODS: Fifty-five AMI patients and 43 control subjects participated in the study. Peripheral blood sampling was performed on days 1, 3, and 7 after AMI. Blood was also sampled from the coronary artery (CAos) and the coronary sinus (CS), before and after acute coronary recanalization. Cardiac expression of PlGF was analyzed in a mouse AMI model.
RESULTS: In AMI patients, peripheral plasma PlGF levels on day 3 were significantly higher than in control subjects. Plasma PlGF levels just after recanalization were significantly higher in the CS than the CAos, which indicates cardiac production and release of PlGF. Peripheral plasma levels of PlGF on day 3 were negatively correlated with the acute phase left ventricular ejection fraction (LVEF), positively correlated with both acute phase peak peripheral monocyte counts and chronic phase changes in LVEF. Placental growth factor messenger ribonucleic acid expression was 26.6-fold greater in a mouse AMI model than in sham-operated mice, and PlGF was expressed mainly in endothelial cells within the infarct region.
CONCLUSIONS: Placental growth factor is rapidly produced in infarct myocardium, especially by endothelial cells during the acute phase of myocardial infarction. Placental growth factor might be over-expressed to compensate the acute ischemic damage, and appears to then act to improve LVEF during the chronic phase.
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Abbreviations and Acronyms
| | AMI = acute myocardial infarction | | CAos = coronary artery ostium | | CK = creatine kinase | | CS = coronary sinus | | flt-1 = vascular endothelial growth factor receptor-1 | | IR = ischemia-reperfusion | | LVEF = left ventricular ejection fraction | | MI = myocardial infarction | | PCI = percutaneous coronary intervention | | PlGF = placental growth factor | | VEGF = vascular endothelial growth factor |
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