A naturally occurring fat molecule reduced heart inflammation and scarring caused by diabetes, thereby improving cardiac function, according to new research. The findings open the door to developing a new treatment for diabetes-induced heart disease.
Diabetes is associated with serious cardiovascular diseases like atherosclerosis (the plaque buildup in the arteries), heart attack, cardiomyopathy, and heart failure. Although the mechanism by which diabetes contributes to cardiac conditions like these isn’t fully understood, persistent inflammation is known to be one culprit.
New research by Monash University in Melbourne, Australia, has identified a naturally occurring fat molecule, lipoxin A4 or LXA4, that can switch off the body’s inflammatory response, preventing chronic inflammation and improving heart function in diabetics. The discovery opens the door to targeted, effective treatments for diabetic heart disease.
“We found that LXA4 could halve inflammation and scar formation, specifically in cases of heart disease induced by diabetes, as seen in the preclinical animal models,” said Dr Cheng Xue Qin from the Monash Institute of Pharmaceutical Sciences (MIPS) and the study’s corresponding author. “With recent advancements in developing more ‘drug-like’ LXA4, our findings point to the potential of LXA4-based therapies as a promising new way to manage diabetic heart disease.”
Healthy inflammation includes the distinct phases of initiation and resolution. During the resolution phase, lipid mediators, including lipoxins, contribute to restoring bodily balance by limiting inflammation. It’s when it doesn’t resolve that inflammation starts to cause problems.
Studies in animals and humans have shown that diabetes is associated with persistent low-grade systemic inflammation due to a class of small proteins called pro-inflammatory cytokines. At the cellular level, inflammation triggers molecular pathways that contribute to an increase in the size (hypertrophy) of cardiac muscle cells (cardiomyocytes), which can negatively affect heart function. So, it made sense for the researchers to investigate whether lipoxins, with their inflammation-resolving properties, would benefit the problematic cardiac inflammation seen in diabetics.
Over six weeks, the researchers administered twice-weekly injections of LXA4 to diabetic mice with cardiovascular disease characterized by heart inflammation, scarring of the heart muscle, dysfunctional cardiomyocytes, increased gene expression associated with cardiomyocyte hypertrophy, and early signs of impaired left ventricular function (the left lower heart chamber, or ventricle, pumps blood to the body) due to muscle stiffening.
“We saw the molecule stimulate reparative macrophages – a type of white blood cell – within the diabetic heart,” said the lead author of the study, MIPS PhD candidate Ting Fu Master. “These good macrophages reduced scar formation (due to chronic inflammation) in the heart and also helped to improve overall function.”
Importantly, the researchers noted that the improvement they observed was independent of blood glucose control. Next, the researchers plan to create a usable LXA4-based drug and investigate whether the molecule could help treat other inflammatory diseases.
The study was published in the journal Cardiovascular Diabetology.
Source: Monash University
