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Protection of damaged hearts with microRNA

<div data-thumb = "" data-src = " The miR-19a / b mice have more heart muscle (green) than a scar (red) Credit: Wang Lab / Boston Children 's Hospital Nature Communications (DOI 10.1038 / s41467-019-09530-1) ">

Protection of damaged hearts with microRNA

Cross sections of the heart two months after treatment. Mice receiving miR-19a / b have more heart muscle (green) in terms of scar (red). Credit: Wang Lab / Boston Children 's Hospital Nature Communications (DOI 10.1038 / s41467-019-09530-1)

Once the heart is fully formed, the cells that make up the heart muscle, known as cardiomyocytes, have a very limited ability to reproduce. After cardiac infarction cardiomyocytes die; Unable to make new ones, the heart forms sharp tissue instead. Over time, this can lead to heart failure.

New work published on April 17th in London Nature Communications advances the ability to revive the regenerative capabilities of the heart by using microRNA molecules that regulate gene function and are abundant in developing hearts.

In 2013, Da-Zhi Wang, a doctor of medicine, a cardiologist at the Boston Children's Hospital, and a professor of pediatrics at Harvard Medical School, identified a microbe family called miR-17-92 that regulates the proliferation of cardiomyocytes. In his new work, his team showed two members of the family, miR-19a and miR-19b, who are particularly powerful and potentially good candidates for heart attack treatment.

Short-term and long-term protection

Wang and colleagues tested the microRNA delivered in two different ways. One method gives them directly mice covered with lipids to help them slip inside the cells. The other method puts the microRNA into a gene therapy vector directed to the heart.

Injectable in mice after a heart attack – either directly in the heart or systemically – miR-19a / b provide immediate and long-term protection. In the early phase, the first 10 days after the heart attack, the microRNA reduces acute cell death and suppresses the inflammatory immune response that worsens cardiac damage. Tests show that these microRNAs inhibit a number of genes involved in these processes.

Longer-term, the treated hearts have more healthy tissue, less dead or labeled tissue and improved contractility, as evidenced by increased left-ventricular fractionation in echocardiography. Broken cardiomyopathy – stretching and thinning the heart muscle, which ultimately weakens the heart – has also been reduced.

"The initial goal is to save and protect the heart from long-lasting damage," Wang said. "In the second phase, we think that microRNAs help to proliferate cardiomyocytes."

One done?

In addition to regulating multiple genetic targets, microRNAs have another advantage as therapy: unlike gene therapy, they do not stay in the heart.

"They enter very quickly and do not last long, but they have a lasting effect in repairing the damaged hearts," says Dr. Jinghai Chen, a former Wang lab author and co-author of Wang paper. (Chen is now the faculty at Institute of Translation Medicine, Zhejiang University, Hangzhou, China.) "We gave the mice only one shot when the heart needed the greatest help, then we continued to check the level of expression of miRNA19a / b After one week the expression decreased to normal level, but the defense goes beyond it every year. "

Even when given systemically, the microRNA is directed to the site of heart damage. But Wang would like to optimize the specifics of the treatment, as miRNAs can affect other tissues and organs. The next step is to test this treatment in a larger animal before proceeding with human studies.

We all do miR-19a / b to some extent, so treatment will stimulate something we already have. "MicroRank has a huge promise to become powerful tools to fight cardiovascular disease," the researchers write.

How the heart sends a SOS signal to the bone marrow cells after a heart attack

More information:
Feng Gao et al., Therapeutic role of miR-19a / 19b in cardiac regeneration and protection from myocardial infarction, Nature Communications (2019). DOI: 10.1038 / s41467-019-09530-1

provided by
Boston Children's Hospital

Protection of injured hearts with microRNA (2019, April 22)
drawn up on 22 April 2019

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