In a heart attack, a series of biochemical processes leave the heart damaged. It is much like a car after an accident.
In the heart attack, the tissues get lost which needs to be rebuilt, proteins that get crushed, muscle damage, and interruptions to blood and oxygen flow to the heart.
Because the heart is not very good at repairing itself, it is important to discover ways to minimize damage in the first place.
Researchers at San Diego State University’s Heart Institute discovered how one key protein in the heart can act as the knight in shining armor, reducing the damage from the attack, which could improve survival rates and heart function in those who do survive.
“The more your heart is damaged, the worse the long-term prognosis, so that’s where our research is focused,” said Chris Glembotski, molecular cardiologist and director of the SDSU Heart Institute.
“We study how to make the heart more resilient to the damage of a heart attack, which would improve patient’s recovery.”
After an attack, many patients have stents put in to open up blocked arteries, which helps in the long term. But the surge of oxygen has drawbacks as well.
“The oxygen surge that occurs as soon as the stent is implanted ‘stuns’ the heart cells and some of them die, which increases irreparable damage to the heart. We found a protein that can minimize the stunning,” said Glembotski.
Glembotski and doctoral candidate Adrian Arrieta found that the protein, MANF (mesencephalic astrocyte-derived neurotrophic factor), acts much like an automobile collision specialist, correcting other proteins that have misfolded.
MANF is among roughly 20,000 proteins in the heart. After Glembotski discovered its potential several years ago, Arrieta was assigned to explore it further.
Arrieta tested genetically modified mice them by inducing a heart attack and observing how they did with and without the protein. They fared much better when MANF was present, acting as a regulator.
“This was our first clue about the importance of MANF in the heart,” Arrieta said. “It has a protective effect, but we didn’t know how it protects, because it is not structurally similar to proteins that we have previously studied.”
Arrieta found evidence that the initial oxidative stress after a heart attack — the overabundance of oxygen — is followed by a potentially damaging opposite effect.
Reductive stress is like an overreaction where oxygen is used by the heart so quickly that it can become depleted.
