Increased Protein Modification Causes Heart Disease in Friedreich’s Ataxia Patients, Study Shows

Increased Protein Modification Causes Heart Disease in Friedreich’s Ataxia Patients, Study Shows

An abnormal increase in protein acetylation leads to heart disease in Friedreich’s ataxia (FA) patients and may represent a new therapeutic target for early intervention, a study finds.

The study “Progressive mitochondrial protein lysine acetylation and heart failure in a model of Friedreich’s ataxia cardiomyopathy,” appeared in Plos One.

The authors found a close relationship between protein acetylation — an important mechanism that alters proteins in order to regulate cellular metabolism — and the metabolic and functional disruption seen in the hearts of FA animal models, as well as in FA patients.

The study used a mouse model of FA, in which mice were genetically modified not to produce the frataxin protein in heart cells, in order to mirror the loss of frataxin seen in FA patients.

Researchers then evaluated changes in the hearts of the animals, both in physiology and function, and documented the disease’s evolution over 30, 45 and 60 days.

Results showed that by day 30, the lack of frataxin caused a rise in the acetylation of proteins in mice heart cells. The rate of this mechanism kept increasing over time, and by day 45, the first abnormal traits of cardiac damage occurred, with thickening of the left ventricular wall and diastolic dysfunction. As acetylation progressed, heart function continued to decline in the mouse models.

Overall, the researchers noticed a strong link between higher protein modification and cardiac fibrosis, mitochondrial damage and impaired metabolism, as well as diastolic and systolic dysfunction leading to heart failure in the animals.

Though this study shows that an increase in acetylation of heart proteins leads to heart damage and disease, no mechanism can yet explain the reason behind this. Study authors urged more research in order to develop new therapies to target early protein acetylation.

FA is a rare inherited disorder affecting about one in every 50,000 Americans. It usually begins in childhood and leads to impaired muscle coordination that worsens over time.

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