by Heart failure, a clinical syndrome characterized by the heart’s reduced ability to pump adequate blood to meet the body’s needs, currently lacks a cure. However, a recent study conducted by researchers from the University of São Paulo (USP) has revealed a previously unknown cellular mechanism that underlies heart failure. Furthermore, they have identified a drug that can reverse the malfunctioning process, potentially improving outcomes for individuals with this condition.
Heart failure is a rapidly growing public health concern affecting an estimated 64 million people worldwide. Despite advancements in treatment, it continues to be associated with high mortality, reduced quality of life, and increased morbidity. The researchers from USP sought to address these challenges by investigating the cellular dysfunction that drives heart failure and identifying a molecule capable of mitigating these effects.
According to the study’s findings, heart failure is associated with malfunctioning mitochondria, which are responsible for producing energy in the body’s cells. The researchers compared this process to a car engine, explaining that when a car engine is not functioning properly, energy conversion is impaired, efficiency drops, and pollution increases. In the case of heart failure, the “pollutant” is a toxic aldehyde known as 4-hydroxynonenal (4-HNE), which is a byproduct of mitochondrial dysfunction.
The researchers discovered that an excess of 4-hydroxynonenal switches off a vital cellular event: the processing of microRNAs. microRNAs (miRNAs) are small RNA molecules that play a crucial role in gene regulation. Disruption of miRNA formation is associated with various diseases, including cardiovascular disorders, cancer, and neurodegenerative conditions.
Through their study, the researchers utilized mass spectrometry to observe that 4-hydroxynonenal irreversibly binds to and inactivates Dicer, an enzyme essential to miRNA formation. This unique mechanism had not been observed before. The researchers identified the chemical alterations that lead to Dicer inactivation and found that heart failure causes an accumulation of aldehyde, resulting in this process.
To investigate potential treatments, the researchers utilized a drug called AD-9308 on human heart tissue samples. The drug successfully restored Dicer activity and reversed the effects of heart failure, leading to improved cardiac function in rodent models. Previous research has also demonstrated that AD-9308 can activate mitochondrial aldehyde dehydrogenase 2 (ALDH2), a major enzyme responsible for detoxifying 4-HNE, effectively treating cardiomyopathy in mice.
AD-9308 stimulates the removal of aldehyde from compromised cells, reducing the likelihood of Dicer being “switched off” and protecting heart cells, explained Julio Ferreira, co-corresponding author of the study. This action helps maintain a microRNA profile closer to that of a healthy heart.
The researchers collaborated with Foresee Pharmaceuticals, a biopharmaceutical company based in Taiwan and the United States, which produces AD-9308. This partnership facilitated the study’s progress and potential therapeutic applications.
In conclusion, the study conducted by USP researchers not only provides new insights into the mechanisms of heart failure but also presents a novel therapeutic intervention that could enhance outcomes for individuals living with this condition.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
Money Singh is a seasoned content writer with over four years of experience in the market research sector. Her expertise spans various industries, including food and beverages, biotechnology, chemical and materials, defense and aerospace, consumer goods, etc.
