Contributor: Steven Stroud
How does the heart clean up after a myocardial infarction? Autophagy. Wong et al identified the role of Cathespin D as a regulator of cardiac remodeling.
First, what is autophagy? Autophagy is derived from the Greek “auto” meaning self and “phagy” meaning eating. Pay close attention, as it is soon to be a familiar term in our field. Exciting new basic and translational research will be presented in CircHF in the coming months.
Healthy autophagy is a process by which the body removes damaged cellular components. As a standard housekeeping activity, autophagy is regulated through ubiquitin tagging of degraded proteins – “ubiquitination” – followed by appropriate proteosomal degradation. Other times it’s unregulated, such as when it is triggered by “starvation” or cellular energy depletion, and cells start literally eating themselves. So too much autophagy – starving cells eating themselves – or too little – degraded proteins remaining in cells and not being cleared – leaves debris that may contribute to myocardial dysfunction.
So, cathepsin D. It is a lysosomal protease that participates in removal of autophagosomes after an infarction. Autophagosomes are organelles involved in autophagy – delivering damaged goods and toxins to the lysosome for destruction.
Explanted hearts of patients with terminal ischemic cardiomyopathy have increased levels of a precursor of cathepsin D. Immediately post myocardial infarction, mice have elevated levels of both mature and precursor cathepsin D. With time, the mature form returns to normal in the mice; however, the precursor form stays elevated, as seen in the explanted human hearts. The pattern of elevated precursor cathepsin D is correlated with increased autophagy. Not just in the infarcted region, but throughout the entire myocardium.
In a heartbeat… Elevated tissue levels of Cathespin D precursor are correlated with autophagic activity in ischemic cardiomyopathy, which may reduce adverse cardiac remodeling and help prevent subsequent cardiomyopathy. Perhaps in the future we will be prescribing pro-autophagy therapy to patients?