Gene mutation responsible for heart disease in young adults: study | Health

Researchers at the University of Maryland School of Medicine (UMSOM) have discovered a novel gene mutation responsible for a rare disease that causes heart attacks in young adults. They were later able to figure out how the mutation worked and apply a drug to counteract its effects on heart muscle cells produced from the patient’s stem cells.

Gene mutations responsible for the disease cause heart attacks in young people: study
Gene mutations responsible for the disease cause heart attacks in young people: study

The findings, published in late April in Circulation, suggest that treatments may be developed to manage the condition rather than requiring a heart transplant, which is the standard treatment for the condition in children.

“Although much has been studied about heart failure in adults, much remains to be learned about the genetic causes of heart failure in infants,” said Charles “Chaz” Hong, MD, PhD, Melvin Sharocki, MD Professor of Medicine and Physiology. Director of Cardiology Research, and Co-Chief of Cardiovascular Medicine at UMSOM. “Mutations in genes we identified were implicated in microcephaly in children but not yet in human heart disease.”

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Infantile dilated cardiomyopathy is a common cause of heart failure – accounting for half of pediatric heart failure cases – the cause of which is often unknown. Although relatively rare, occurring in about one in 200,000 births, babies with this condition have hearts that fail to contract effectively, so they are not able to pump as much blood as they should.

Dr. The genetic mutation discovered by Hong and his colleagues was found to make a protein normally found in the cell structure, the centrosome, which acts as a tether for the cytoskeleton and is best thought of for its role during cell division.

Without this protein, heart muscle cells were unable to organize themselves properly and would not contract, which affected the heart’s pumping, the researchers theorized.

“We initially dismissed our findings as an artifact that the cell division machinery would be involved in this type of heart muscle work,” Dr. Hong said. “We thought that once heart cells matured, this cell division machinery would disappear completely, but it turns out, it moves to a new location in the cell and takes on a new role in heart muscle function.”

To identify the gene mutation responsible for the infant’s heart failure, the researchers removed a sample of heart cells from the patient’s diseased heart after it was removed during a transplant. They then transformed this heart tissue into stem cells, so they could grow more cells and study them in the lab. They determined that the patient had two different mutations of the gene, one from each parent, that normally encodes for the rotatin protein.

When the researchers removed this protein from the hearts of zebrafish, those hearts showed signs of heart failure. The researchers also looked at fruit fly hearts missing rotatin and found that the muscle cells in these hearts were disorganized and did not contract as well as they did, as occurs with the disorder in a baby’s heart.

“This is the first human disease caused by a mutation in the centrosome structure that usually appears shortly after birth,” said Matthew Miyamoto, first co-author who worked on the project as a second-year medical student. Hong’s laboratory.

The researchers then used C19, a drug known to organize centrosomes, in developing heart muscle cells derived from a patient with infantile dilated cardiomyopathy. The drug restored the organization of the developing heart muscle cells grown in the dish from the patient’s stem cells and their ability to contract.

“Because centrosomes play such a fundamental role in cardiac muscle development, particularly in cell replication, structure, and function, a better understanding of this tissue-specific programmed process will be highly relevant to future cardiac regenerative treatment efforts,” said UMSOM Dean, Mark T. Gladwin, MD, Director of Medical Affairs, University of Maryland, Baltimore (UMB), and John Z. and Akiko K. Bowers is also the vice president for distinguished professors. Dr. Hong added, “It is only the collaboration between cardiologists, medical student trainees, and laboratory researchers that has allowed this biomedical discovery that we hope will one day translate into medical treatments for children with this condition.”

Patrice Desvigne-Nickens, MD, a medical officer in the Heart Failure and Arrhythmias Branch at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, agrees. “This study makes an important contribution to understanding the biological basis of infantile dilated cardiomyopathy and its association with heart failure,” she said. “We look forward to future studies to clarify and confirm these findings in an effort to improve heart failure outcomes.”

This story is published from the Wire Agency feed without modification to the text. Only the headline has been changed.

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