PlGF involved in Post Myocardial Infarction Healing Process
Apr 15, 2006 - 6:29:37 PM
Heart attack patients produce higher levels of a natural substance in the body that plays a role in the growth of new blood vessels and this over-expression of placental growth factor (PlGF) may help reduce damage to the heart muscle, according to a new study in the April 18, 2006, issue of the Journal of the American College of Cardiology.
"Because the degree of PlGF production released from the heart after a heart attack correlated with the improvement of cardiac function, we think PlGF becomes a potential treatment of myocardial infarction. Furthermore, previous studies have shown that PlGF enhances angiogenesis and arteriogenesis in ischemic tissue, also PlGF appears to promote mobilization of flt-1-positive hematopoietic stem cells from bone marrow to the peripheral circulation. We have started further experiments to evaluate this hypothesis," said Shiro Uemura, M.D. from the Nara Medical University in Kashihara, Japan.
The researchers, including first author Hajime Iwama, M.D., compared 55 heart attack patients to 43 control subjects. The heart attack patients had significantly higher levels of PlGF than the healthy subjects. Also, the patients with higher levels of PlGF three days after a heart attack had lower left ventricular ejection fractions, indicating more heart muscle damage. The researchers wrote that it is likely that the degree of injury is a key determinant of how much PlGF the body produces.
Dr. Uemura said it appears that PlGF is involved in the healing process after a heart attack, including the mobilization of stem cells
"From these results, it seems likely that cardiac production of PlGF promoted the mobilization of bone marrow derived monocytes, possibly including endothelial progenitor cells, which might be involved in tissue repair of injured myocardium," he said.
The researchers also performed an experiment on laboratory mice. They found that in mice that underwent a procedure that interrupted coronary blood flow, similar to what happens during a heart attack, PlGF levels shot up to 23 times the levels seen in control mice.
Although the researchers say their results suggest that PlGF should be studied as a potential heart attack treatment, they pointed out that studies of a similar substance, called VEGF, produced some disappointing results. Although early studies indicated that VEGF could spur the development of new blood vessels (angiogenesis), many of the new blood vessels did not work properly.
"The possibility of VEGF treatment for heart attack has been extensively studied because of its established angiogenic capacity, but previous in vivo studies with VEGF gene or recombinant VEGF protein were not always successful in the preservation of ventricular function because of the development of non-functioning or unstable capillary vessels. On the other hand, PlGF is previously reported to enhance not only capillary, but also collateral formation in ischemic tissue. According to our observation in this study, we speculate that PlGF becomes the alternative molecule to enhance tissue repair after acute myocardial infarction,"
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