PROTEIN DISCOVERED TO HAVE MAJOR ROLE IN HEALING THE HEART!

Glycoprotein Non-Metastatic Melanoma Protein B( GPNMB) was discovered to be a prime regulator in repairing the heart after heart attack by UCLA scientists

Cardiac cells surrounding damaged tissue after

an attack. Credit: Arjun Deb lab/ UCLA

As one of the leading causes of death in the globe, heart attacks, or more formally, myocardial infarctions have long puzzled doctors and scientists in developing effective recovery treatments. Essentially, patients tend to physically deteriorate after a heart attack, as the heart weakens due to extensive damage and fibrosis (scarring).  

However, recent discoveries on a protein released by macrophages (white blood cells) might change the outlook on recovery.

WHAT IS GPNMB AND WHERE IS IT FOUND?

GPNMB is a protein that is embedded in the cell membrane, and in this case, of white blood cells produced by the bone marrow. 

WHY CONDUCT A STUDY OF THEM IN THE FIRST PLACE?

Previous studies have shown that GPNMB is strongly linked with cardiovascular outcomes of people who have experienced heart failure. However, it was not explicitly clear whether the absence of  GPNMB directly resulted in the development of heart failure after a heart attack. 

Given the strong association with cardiovascular outcomes, GPNMB's role in heart recuperation warranted further research. 

The knowledge of GPNMB's influence on heart failure after heart attacks could be critical in procuring a medical treatment in which GPNMB is used to aid the healing process of the heart after a patient experiences an attack.

WHAT HAPPENED IN THE STUDY?

Using mice, the scientists proved that GPNMB was not produced by the heart itself but rather through white blood cells from the bone marrow. After the myocardial infarction, these cells migrate to the heart, where they generate GPNMB.

Thereafter, they conducted a gene knockout where, basically, scientists had one group of mice in which the gene which produces GPNMB in the white blood cells is inactivated. As a result, there was a higher occurrence of heart rupture in that group.

In contrast, another group of mice, with an active GPNMB gene and where the levels of GPNMB are normal, an extra dose of GPNMB was administered. Consequently, this group exhibited limited heart scarring and better function. 

4 weeks after stimulating heart attacks in mice from both groups, it was evident that the group without GPNMB degraded immensely after post heart attack whilst the control group recovered well.  Two-thirds of the mice without the GPNMB gene displayed severe scarring while only 8% of the mice with GPNMB gene showed severe scarring. 

Moreover, the scientists uncovered that GPNMB binds to a receptor, which binding partner was previously unknown, called GPR39. The binding results in a series of chemical reactions which causes tissue reformation and reduce the extent of scarring. 

MECHANISM OF HEALING PROCESS?

GPNMB is a transmembrane protein. Imagine sticking a pin partially into a ball. One part of the pin is outside the ball, another part is in the skin of the ball, whilst the remaining part is inside the ball. Now transfer this image to the setting of a cellular environment where the GPNMB is the pin while the white blood cell is the ball. This is essentially how a transmembrane protein would be positioned

During an heart attack, the white blood cells, produced by the bone marrow, migrate to the heart. Thereafter, a bunch of enzymes cuts off the outside part of GPNMB whilst the 2 remaining parts remain attached to the cell. The cleaved part moves away from the white blood cell and then binds to GPR39, which is also a transmembrane protein, on another cell. This binding initiate signaling pathways that promote tissue repair and limit scarring

This process of cleaving the outside part of GPNMB and the cleaved part interacting with the GPR39 receptor is called Paracrine Signaling. Perhaps I could make an article in the future about Paracrine Signaling to delve deeper into it!

CLINICAL APPLICATION

So far, GPNMB as a therapeutic solution to improving the recovery of heart attack patients has not been assessed in human clinic trials as further research would be required to confirm its safety against human subjects.

However if successful, it possibly could be used to improve the healing process in patients and, as a result, lead to a better physical lifestyle with patients as lower scarring of the heart leads to less strain on the heart when pumping blood around the body, decreasing the risk of further damage over time. 

Anyways, feel free to comment down in the comment section below, about your opinions of this discovery and what I could talk about next! 

REFERENCES

1. ScienceDaily. (2024, October 25). The new study demonstrates the therapeutic potential of GPNMB in tissue repair. ScienceDaily. https://www.sciencedaily.com/releases/2024/10/241025122619.htm

2. ScienceDirect. (n.d.). Paracrine signaling. ScienceDirect. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/paracrine-signalling