A new study reveals that oxygen is the trigger that helps specific genes in heart cells called cardiac fibroblasts transform these cells into myofibroblasts - cells that are critical to wound healing - after a heart attack. Scientists believe these newly formed myofibroblasts help new tissue grow, replacing tissue damaged by the attack.
The first step in treating a heart attack survivor is to quickly remove the clot blocking a coronary artery which caused the attack. This allows a sudden rush of oxygen-rich blood to flow into damaged tissue around the site of the primary injury.
The rush of oxygen activates oxygen-sensitive genes in cardiac fibroblasts, and these genes respond by turning cardiac fibroblasts into myofibroblasts, said Chandan Sen, the study's lead author. Sen is the associate director of the Dorothy M. Davis Heart and Lung Research Institute at Ohio State
"Now that we've identified the mechanism in this band of cells, we may be able to develop therapies that target these healing cells, thus enhancing their ability to replace the tissue damaged during a heart attack."
The study currently appears online in the Journal of Biological Chemistry.
The researchers exposed fibroblasts taken from mouse hearts to a sudden rush of oxygen, a situation that mimics suddenly exposing heart tissue with a poor blood supply to more oxygen once a clot has been removed.
The sudden rush of oxygen transformed mouse heart fibroblasts into myofibroblasts.
"Myofibroblasts go to work after you cut yourself," Sen explained. "They have muscle-like properties and try to contract and close a wound. These are robust cells -- they remain at the damaged site even when all of the heart muscle cells have died.
"Other scientists have detected an abundance of myofibroblasts in heart tissue after a heart attack," he continued. "But our study is the first to suggest the mechanism behind this differentiation -- that a sudden exposure to higher oxygen pressure causes significant changes in the gene expression, looks and function of cardiac fibroblasts."
A heart attack occurs when a clots form, blocking blood flow through a coronary artery. Since a clot develops over time, heart cells slowly adjust to chronic hypoxia - a condition of severely reduced oxygen levels. Heart cells have a tremendous ability to survive under low-oxygen conditions, said Sen, adding that sudden re-oxygenation of the tissue at the site of the clot can result in cell injury or death.
"The injured tissue is like a bull's-eye," Sen said. "This area is the most shocked by a rush of oxygen-rich blood.
"Imagine a series of concentric circles surrounding the damage - oxygen shock progressively lessens the further you move away from the bull's-eye," he continued. "While the tissue in the bull's-eye is the most shocked and the heart cells here die, the shock at the perimeter of the damage is not lethal.
"This shock at the perimeter serves as a wake-up call to trigger healing. And now you have a healing band of tissue around the injured site."
It's this band of newly formed myofibroblasts that can help the heart replace tissue killed by the heart attack.
"It is important to appreciate that the heart has a built-in, healing component," Sen said. "Focusing on this healing band of tissue at the perimeter of the damaged site is likely to provide effective therapeutic solutions."
He conducted the study with Jay Zweier, Director of the Dorothy M. Davis Heart and Lung Research Institute at Ohio State; Sashwati Roy, Savita Khanna, William Wallace, Jani Lappalainen, Cameron Rink, and Arturo Cardounel, all with the Davis Heart and Lung Research Institute.