Scientists have demonstrated that saturated fats have detrimental effects on heart health, but omega-3 fatty acids such as EPA have a protective effect.
A recent study by a Japanese research team reveals how EPA helps maintain calcium homeostasis in cardiac cells disrupted by saturated fat, and involves key pathways and regulatory proteins that may help guide future dietary recommendations and health guidelines.
Over the past few decades, scientists have produced a mountain of evidence suggesting that a diet high in saturated fat may be enough to cause heart disease. In addition to problems like diabetes and atherosclerosis, saturated fat has also been linked to life-threatening cardiac arrhythmias.
Interestingly, based on animal and human studies, certain omega-3 polyunsaturated fatty acids appear to have beneficial effects on cardiovascular health, particularly eicosapentaenoic acid (EA). acid EPA, found in fish oil, not only has vasodilatory and antiplatelet effects but also helps prevent atrial fibrillation and other arrhythmias. Although EPA is readily available as a dietary supplement, the effects of EPA on cardiomyocytes and its underlying mechanism of action have not been fully elucidated.
New Research on EPA’s Effects on the Heart
In a study recently published online in the International Journal of Molecular Science, a team of Japanese researchers set out to fill this knowledge gap. Led by Associate Professor Masaki Morishima of Kinki University, the team used a variety of bioanalytical techniques to investigate the role of EPA in inducing long-term electrical changes in cultured mouse cardiac myocytes. The research paper was co-authored by Dr. Katsunari Ono of Oita University and Dr. Kazuki Horikawa of Tokushima University.
The main focus of this study was how oleic acid/palmitic acid mixture (OAPA), a well-studied saturated fat, affects calcium homeostasis in cardiomyocytes by acting on Ca2+ ion channels, and whether EPA could rescue these changes and restore normal function.
Mechanism by which EPA protects cardiac cells
First, the researchers used real-time PCR to find that OAPA significantly reduced the mRNA levels of Cav1.2 L-type Ca2+ channels, and a live-cell imaging system confirmed that OAPA also reduced the spontaneous beating rate of cardiomyocytes.
Remarkably, the combination of OAPA with small amounts of EPA prevented these changes and restored both Cav1.2 mRNA and protein expression levels. By electrophysiological measurements, the researchers confirmed that EPA also prevented the decrease in Cav1.2 channel current caused by OAPA.
Advanced insights and future impact
To gain more insight into the effects of OAPA and EPA, the team next looked at a transcription factor called cAMP response element-binding protein (CREB), whose phosphorylation is an indicator of Cav1.2 transcription. OAPA reduced CREB mRNA in a manner that was in perfect agreement with the changes in Cav1.2 mRNA, while EPA was able to prevent these changes.
The researchers next turned their attention to the EPA receptor, FFAR4. Interestingly, they observed that an FFAR4 agonist, which mimicked the effects of EPA, restored the changes caused by OAPA, whereas an FFAR4 antagonist completely inhibited the effects of EPA. Together, these findings revealed that EPA is involved in the regulatory pathway mediated by FFAR4, affecting the regulation of L-type Ca2+ channels in cardiomyocytes.
A final series of experiments revealed that OAPA causes oxidative stress through the accumulation of reactive oxygen species. seed Again, EPA can rescue OAPA-induced ROS accumulation. However, ROS accumulation was found to affect Cav1.2 L-type Ca2+ channel transcription through a different pathway that is independent of FFAR4.
Taken together, this study sheds some much-needed light on the underlying mechanisms by which EPA can enhance heart health. “Although there are techniques and drugs to control arrhythmias, there is no established method to prevent them,” says Dr. Morishima. She adds: “Our findings suggest that EPA has a protective effect on myocardial cells by normalizing the abnormalities caused by excessive intake of saturated fatty acids, which occurs in a high-fat diet.”
The research team anticipates that these findings will pave the way for smarter dietary choices and new health guidelines. “Research into nutrients and disease prevention takes a long time, but studies like ours lay the foundation for practical nutritional strategies that can be seamlessly integrated into daily diets,” concludes Dr. Morishima, hoping for a healthier future.
Reference: “Eicosapentaenoic acid rescues saturated fatty acid-induced depression of Cav1.2 L-type Ca2+ channels in cardiomyocytes via both free fatty acid receptor 4-dependent and -independent pathways,” Masaki Morishima, Pu Wang, Kosuke Horii, Kazuki Horikawa, Katsushige Ono, July 9, 2024, International Journal of Molecular Sciences.
Translation: 10.3390/ijms25147570
