EPO Improves the Efficiency of EPC Treatment After a Heart Attack

I have just written about the abuse of EPO (erythropoietin) by the professional cyclist Lance Armstrong. However, commercial EPO has legitimate medicinal uses. It is given to cancer patients who have very low red blood cell counts after chemotherapy, and to those who suffer from chronic anemia. EPO might also increase healing after a heart attack, and several experiments seem to provide evidence for this conclusion,

EPCs are stem cells programmed to become blood vessels. They repair blood vessels and make new ones. When EPCs are transplanted into an animal or human heart after a recent heart attack, they make new blood vessels, which help feed and repair the damaged heart muscle, and improve circulation of the heart in general. The problem with transplanted EPCs is that the vast majority of them die soon after transplantation.
EPO, however, has the useful capability of prevent cell death. EPO activates several signaling pathways inside the cell that increases cell survival and viability. Therefore, a Chinese group has examined the ability of EPO to increase the survival and therefore the utility of EPC treatment after a heart attack in laboratory animals.

Yan Cheng and colleagues at Jinling Hospital at Nanjing University School of Medicine in Nanjing, China used mice labeled with a gene that makes their cells glow. They isolated bone marrow from these mice and teased from this bone marrow EPCs, which is not as easy as it sounds. Then they induced heart attacks in a different mouse strain whose cells do not glow. Into one group, they transplanted 50,000 glowing EPCs. Into another mouse group, they transplanted only buffer as a control. Into the third group, they transplanted 50,000 EPCs and gave 20 units of EPO. Into a fourth group, they gave only 20 units of EPO. All cells were transplanted with a small needle, directly into the heart muscle.

The mice were assessed in several ways. The cells were viewed in the hearts of the mice to determine if they had survived. Mice were also given an electrocardiogram to determine if the electrical activity of the heart was normal. Hearts were also assayed to determine is the number of blood vessels increased and if the heart scar changed during the course of treatment. Finally, mice were checked to see how many cells had died in the hearts of the mice.

28 days after transplantation, no detectable EPCs were seen in those mice that only received EPCs. Apparently, all the transplanted cells have died. Those mice that had received EPO and EPCs, had detectable EPCS in their hearts after 4 weeks. Also, the EPC + EPO-treated mice had far more EPCs in their hearts after 7 days and the death of those cells was much less precipitous than in those mice treated only with EPCs and no EPO.

Another group of chemicals measured in the hearts of these animals are those that summon stem cells to the heart. 7 days after the transplantations, the EPO + EPC-treated mice had more of those stem cell-summoning chemicals in their hearts, but by 28 days after transplantation, those differences had disappeared. Also,

ECGs of mouse hearts confirmed that those mice treated with stem cells had healthier hearts than those who did not, but the mice that received EPO + EPCs had even better ECGs than the rest. This shows that the functional recovery of those mice that had received EPCs and EPO was accelerated relative to the other mice.

Finally, the level of scarring was decreased in all categories of mice relative to the controls, but the EPO + EPC-treated mice had the lowest amount of heart scarring. This demonstrates the ability of EPO to augment EPC therapy after a heart attack in laboratory mice.

This study suggests that there is a synergy between EPO and EPCs in healing a heart after a heat attack. EPCs have been used experimentally in human heart attack patients, but little has been done with EPO in heart attack patients in humans. Various commercial types of EPO have been dropped from the market because of their tendency to induce heart attacks. Increasing the red blood count sometimes increased the blood volume and that can be too much for heart patients, and high blood pressure and congestive heart failure are two possible side effects of erythropoietin. In kidney patients, high dose erythropoietin can prompt to onset of kidney failure. However, at the dosages of EPO used in these experiments, it is doubtful that this will be an issue. 20 units of EPO for a 22-28-gram mouse is less than the 300 units/kg body weight 3 times weekly dosage for clinical purposes. Therefore, it seems unlikely that this treatment would produce the side effects of continued high-dose EPO.

Therefore, we have a strategy for heart attack patients that seems to work well in mice. Further pre-clinical work is required, but should this pan out, human trials will hopefully evaluate this strategy in human patients dome day soon.