How the MANF Protein Could Revolutionize Recovery from Heart Attacks

Researchers at San Diego State University have just identified the MANF protein which can help regulate the flow of oxygen and blood in the heart after a heart attack.

Heart Attack

Heart Attack

Myocardial infarction or heart attack, which affects almost 805,000 Americans every year, is caused by fatty deposits on the walls of arteries that block the flow of blood to the heart, depriving it of oxygen and damaging the heart muscle (the myocardium).

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Under oxygen deprivation, the cells of the heart muscle become necrotic and die, which can lead to death: This is the case in 10% of heart attacks. But even if the patient survives, his heart is severely damaged. Tissue must be rebuilt and muscle damage repaired to restore blood and oxygen flow.

A discovery by researchers from the Heart Institute at San Diego State University could help repair damaged hearts faster after a heart attack. In a study published in the Journal of Biological Chemistry, they explain that they have identified a key protein in the heart that can reduce the damage caused by a heart attack. Its use can improve the survival rate and heart function of people who have suffered a heart attack.

A reduction in oxidative stress

After a heart attack, many patients get stents to open blocked arteries and supply the heart with oxygen. However, the use of stents has disadvantages: The increased oxygen level that is created when the stent is inserted “shocks” the heart cells, and some of them die, increasing the irreparable damage to the heart. “We have found a protein that can minimize this,” says Chris Glembotski, molecular cardiologist and director of the Heart Institute at San Diego State University.

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This protein, called MANF (mesencephalic astrocyte-derived neurotrophic factor) corrects the effects of other malfunctioning proteins after a heart attack. The MANF protein, which was successfully tested in genetically modified mice, reduces the damage induced by oxidative stress, i.e. the excess oxygen after a heart attack.

The researchers now hope that this discovery could lead to intravenous administration of the protein in the first moments after a heart attack. “One of our most interesting findings is that MANF is a chaperone protein that keeps other proteins functional during oxidative stress. If we could administer more MANF to the heart attack victims, they would have less damage after a heart attack and recover more quickly,” says Adrian Arrieta, a researcher who participated in the study.

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The next task of the scientific team will be to investigate the effect of the protein in the heart of pigs that react like human hearts after a heart attack. They will also look for optimal ways to administer MANF to the heart, again in laboratory animals, as this is a crucial step in the development of MANF as a drug for humans.


Arrieta, A., Blackwood, E. A., Stauffer, W. T., Sarakki, A. V., Doroudgar, S., & Glembotski, C. C. (2020). Mesencephalic astrocyte–derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart. Journal of Biological Chemistry, 295(22), 7566-7583.



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