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A group of researchers from Brazil and the United States has developed a molecule that slows the progression of heart failure and even improves its ability to pump blood.
Rats with heart failure treated for six weeks with the molecule, known as SAMbA, not only exhibited stabilization of the disease – as with current drugs – as they still exhibited a regression of disease. Heart failure can occur as a result of a myocardial infarction, when an obstructed coronary artery prevents the supply of blood to one part of the heart, overloading the rest of the tissues. As a result, the organ reduces its ability to pump blood to the body over time.
Researchers have already applied the molecule and its application in the United States. It could eventually supplement or even replace the current drugs used against heart failure, most of them created in the 1980s.
The study presenting the description of the molecule was published in Nature Communications . The name SAMbA is an acronym in English for Selective Antagonist of the Association of Mitofusina 1 and Beta2PKC. SAMbA has the ability to prevent the interaction between a common protein of the cardiac cell, Kinase Beta 2 protein (Beta2PKC), and Mitofusin 1 (Mfn1), located inside the mitochondria , the cellular compartment responsible for the production of energy [19659002] When they interact, Beta2PKC cuts Mfn1, thus preventing the mitochondria from producing energy and thus decreasing the ability of cardiac muscle cells to pump blood.
"One of the important results of this work was precisely this interaction it was not known to be critical in the progression of heart failure," said Julio Cesar Batista Ferreira, professor at # 39; Institute of Biomedical Sciences of the University of São Paulo (ICB-USP) and head of the study. Ferreira started researching the theme in 2009, even during the postdoctoral year at the School of Physical Education and Sports of the University of São Paulo with a Fapesp scholarship.
After the filing of the patent, the researcher hopes that the molecule can be tested in other cardiovascular diseases in addition to heart failure because it could have an action in pathologies such as lymphatic diseases. ;hypertension.
"We suspect that the interaction between these proteins is, in general, a conserved process in other degenerative diseases with mitochondrial dysfunction," Ferreira said.
Office Clerk and Director
In previous work, the team led by Ferreira at ICB had demonstrated that the inhibition of Beta2PKC, which is produced in excess in the cell suffering from the disease. heart failure, improved cardiac function by insufficiency. The novelty of the SAMbA molecule is that it selectively inhibits the interaction of Beta2PKC with Mfn1 present in mitochondria. Other interactions continue to occur.
To explain the difference, Ferreira makes an badogy. The heart cell would be like a business with multiple rooms. The Beta2PKC crosses the lobby of this company and enters different rooms interacting with officials of the corresponding sector to perform their work.
However, every time he enters a specific room (mitochondria), the office attendant (Beta2PKC) a specific manager (Mfn1) to work. In the first molecule developed by the group, it was as if the doors of each room were closed. The office boy no longer disrupted the mitochondrial responsible, but he did not go to another room either and the company (the heart cell) did not function harmoniously.
SAMbA only prevents the interaction of Beta2PKC with the current Mfn1. in the mitochondria. "It's like closing the door of the room where the official should not enter, leaving him free to enter the others, thus leaving the company in full operation," Ferreira said.
Infested rats
To achieve SAMbA, tests were performed with recombinant proteins, cells, animals, and human heart tissue samples with heart failure
The researchers first performed various in vitro tests of interactions between Beta2PKC and Mfn1. In total, it turned out that six molecules exhibited inhibition, but only SAMbA selectively did so only in the interaction between Beta2PKC and Mfn1.
SAMbA was then tested on human heart cells. In addition to curbing the progress of the disease, just like the drugs currently used, the molecule has improved the ability of the cell to contract (essential for pumping blood from the heart to the rest of the body).
The molecule also decreased the amount of mitochondria in the cardiac cell. The presence of this peroxide characterizes oxidative stress, a signal that maximizes the degeneration of the cardiac cell.
Finally, the researchers induced myocardial infarction in the rat. After a month, their heart had an image of heart failure. Each mouse then received a device under the skin, called osmotic pump, which released small amounts of SAMbA, or a harmless substance used as a control, for six weeks.
Unlike mice that received the control substance, SAMBA not only blocked the disease, but also improved its cardiac function.
"The current drugs slow down the progression of the disease but never make it regress, we show that by regulating this specific interaction, the progression is slowed down and always brings the disease to a lighter stage," said Ferreira.
The next step is to make the SAMbA molecule available to other research groups for testing. in different diseases and experimental models. In addition, it is necessary to test the interaction of the molecule with other drugs currently used in the treatment of heart failure.
"Validation and replication of results from other groups is critical to the development of SAMbA as a possible treatment for heart failure.According to the World Health Organization, cardiovascular diseases make 17.9 million deaths per year, or 31% of the total deaths worldwide, according to Ferreira
.Generally, the myocardial infarction and the resulting heart failure remain morbidity and mortality factors major.
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