Thursday , April 22 2021

Researchers create new molecules for the destruction of heart cities



The molecule also has the capacity of peroxide in the & gt; mitochondria of & # 39; a heartbeat diminish. The presence of this peroxide characterizes the so-called oxidative stress, a signal that maximizes the degradation of the heartbeat.

A group of researchers from Brazil and the United States have developed a molecule that fails the potency of heart failure and even improves the heart's ability to pump blood.

The resuscitation mouse treated for six weeks with the molecule called SAMbA not only presents a stabilization of the disease – as with current medication – but also had a regression of & # 39; conditions. The animals had an improvement in & # 39; a heartbreak.

Heart rate can occur as a consequence of a myocardial infiltration, as a wounded short-term artery prevents blood from occurring to part of the heart, overloading the weight of the weight. As a result, the organ limits its ability to pump blood into air over time.

The researchers have already applied for the patent for the molecule and its application in the United States. It can eventually replace the current medications or even replace them with the heartbeat, most of them originating in & # 39; years & # 39; 80.

The study with the description of the molecule is in & # 39; e published Nature Communications. The name SAMBA is an acronym in & # 39; t English for Selected Antagonist of & # 39; an association of Mitofusina 1 and Beta2PKC. SAMBA has the ability to prevent the interaction between a common protein in heart cells, Kinase Beta 2 (Beta2PKC), and Mitofusin 1 (Mfn1), which is inside the mitochondria, responsible for the cell box to make energy.

When interacted, Beta2PKC stops Mfn1, preventing mitochondria from making energy and hence the ability of heart muscle cells to drain blood.

"One of the important findings of this study was precisely this interaction, which was not known to the criticism in & # 39; the progress of the fall," he said. Julio Cesar Batista Ferreira, professor of the Institute for Biomedical Sciences of São Paulo University (ICB-USP) and leader of & # 39; a study. Ferreira started the research on the theme in 2009, yet in & # 39; post-doctoral to & # 39; a School of Physical Education and Sports or USP FAPESP point.

After the patent is filmed, the researcher hopes that the molecule may be in other cardiovascular diseases despite heart failure, as it may have action in padenology such as hypertension.

"We think the interaction between these barges is generally a conserved process in other degenerative diseases that have dysfunctional dysfunction," Ferreira said. FAPESP Agency.

Office boy and manager

In previous work, the team led by Ferreira at the ICB has demonstrated that an inhibition of Beta2PKC, which is in remnant's production with heart, improves heart function with inability. However, the intervention avoids other functions of the eau, beneficial for the functioning of the heart organ.

The short story of the SAMbA molecule is that it selects the Beta2PKC interaction with Mfn1 present in mitochondria. Listen to the other interactions.

To explore the difference, Ferreira refers to an analogy. The cardiological cell would be like a company with several rooms. Beta2PKC runs through the corridor of this company and comes in different rooms, interacting with the manager of the particular sector to perform his work.

Every time it comes to a course fee (Beta2PKC) for a specific room (the mitochondria) of a work trainer (Mfn1). Developed in the first molecule by the group, it was as if the doors of each room were closed. The office did not come in a way from & # 39; a mitochondria manager, but he also did not go to another room and the company (the hartels) did not work harmoniously.

What SAMbA does is only prevent the presence of Beta2PKC with Mfn1 in Mitochondria. "It just seems to be the door of the room where the kitchen does not come in, and he asks for free to ask the others to keep the company in full operation," Ferreira said.

Infarcted rat

In order to reach SAMbA, tests performed with recombinant experiments, cells, animals and tissue problems from human hearts were resuscitated.

First, the researchers did several tests in vitro of interactions between Beta2PKC and Mfn1. In total, six molecules were found to be inhibited, but only SAMbA selected it only in the interaction between Beta2PKC and Mfn1.

Then, SAMbA was examined on human cardiovascular drugs. In addition to the & # 39; deletion of & # 39; A disease, like the medicine currently used, has improved the ability of the cells to improve the cells (it is essential to cripple blood from the heart to the rest of the body).

The molecule also has the capacity of peroxide in the & gt; mitochondria of & # 39; a heartbeat diminish. The presence of this peroxide characterizes the so-called oxidative stress, a signal that maximizes the degradation of the heartbeat.

Eventually, the researchers have myocardial infection in rats. After a month, her heart had an image of heartfeltness. Each rat was then given a device under the skin, which was called the osmotic pump, which used a whole measure of SAMbA, or an innocent substance for control, for six weeks.

Originally from the mouse that received the control substance, those who had received SAMBA had not only blocked the disease, but also improved cardiovascular function.

"Today's drugs shut down the onset of illness, but they never go away. What we show is that by regulating this specific interaction, progression is slipping and neither is the disease going to a lighter stage", Ferreira said. .

The next step is to make SAMbA molecules available to other research groups so that it can investigate various disease and experimental models. In addition, it is necessary to check the interaction of your molecule with other medicines that are currently used in & # 39; a stroke treatment.

"The validation and reproduction of findings by other fractions is critical in the development of SAMbA as a potential terapy in heartbeat. For this, search for partners from our private and public sectors is needed," said Ferreira.

Cardiovascular disease causes 17.9 million people annually, 31% from & # 39; a world, according to the World Heritage Organization. In total, oral and heart defects resulting from this are still major morbidity and mortal factors.

The article A selective inhibitor of Mitofusin 1-βIIPKC association improves heart rate outcomes in rates (doi: 10.1038 / s41467-018-08276-6) de Julio C.B Ferreira, Juliane Campos, Nir Qvit, Xin Qi, Luiz H.M. Bozi, Luiz R.G. Bechara, Vanessa M. Lima, Bruno B. Queliconi, Marie-Helene Disatnik, Paulo M.M. Alicia J. Kowaltowski and Daria Mochly-Rosen can be read in www.nature.com/articles/s41467-018-08276-6.


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