NOV 23, 2016

"BAG3" Protein Protects the Heart From Irreparable Damage

WRITTEN BY: Kara Marker
As if a heart attack weren’t traumatic enough, the tissue injury that follows can cause irreparable damage to heart muscle, increasing an individual’s risk of heart failure occurring later. With the discovery of a new role for a known protein, though, scientists are one step closer to limiting tissue injury and reducing risk of further heart problems.
Reperfusion injury, or the “inability of cells to eliminate damaged proteins and organelles” after a coronary artery is blocked and then re-opened, either with angioplasty surgery or with drugs, creates dysfunctional organelles that lead to the release of toxic oxidizing substances when oxygen-rich blood returns to the heart. Toxic oxidizing substances activate cell death pathways and limit the rate of autophagy, a cleaning process that removes faulty proteins and organelles from the cell.

Coming to the rescue, though, is Bcl-2-associated athanogene 3 (BAG3), a protein showed in a new study to help limit reperfusion injury.  Enhancing the expression of BAG3 could prevent all of these bad things from happening, according to a new study from scientists at Temple University. New findings suggest that BAG3 could be the center of new therapeutics for reperfusion in heart attack patients.

BAG3 expression is beneficial by inactivating cell death pathways and activating autophagy, essentially reversing the negative influence of the toxic oxidizing substances produced after damage is done to the heart muscle. Scientists saw this effect in cultured cardiomyocytes during their study.

"After finding that a mutation in BAG3 caused heart failure in a Philadelphia family, we have been trying to figure out what the protein does in the heart," said senior investigator Dr. Arthur M. Feldman, MD, PhD, on how his team got to the results they found in the present study.  "Now that we have a better understanding of its role and what happens when its levels are increased, we can investigate the possibility of targeting BAG3 in human patients using gene therapy or a small molecule."

Feldman’s study was recently published in the journal JCI Insight.
 


Source: Temple University Health System