'No.1 Cause of Sudden Death' Myocardial Infarction Treated by Regulating Immune Response

KIST-Catholic University Research Team
Develops Treatment for Severe Myocardial Infarction Previously Untreatable

A new method to treat myocardial infarction, the leading cause of sudden death among adults in Korea, through immune response regulation has been developed.

The Korea Institute of Science and Technology (KIST) announced on the 6th that the research team led by Senior Researcher Yoon-Ki Jeong of the Center for Biomaterials and Dr. Joo-Ro Lee, in collaboration with The Catholic University of Korea, developed a new myocardial infarction treatment method that regulates immune responses using nanovesicles derived from apoptotic fibroblasts.

Myocardial infarction, which is also the second leading cause of death, has an initial mortality rate of 30%. Even when patients are transported to medical institutions and treated, about 5-10% still die from this fatal disease. In particular, the number of patients in Korea has sharply increased by 26.8% over five years, from 99,647 in 2017 to 126,342 in 2021. Until now, drug therapy, percutaneous transluminal angioplasty, and coronary artery bypass surgery have been known as treatment methods, but these were difficult to apply to severe cases that do not respond to such treatments.

Myocardial infarction is an ischemic heart disease caused by narrowing or blockage of the coronary arteries, which supply blood to the heart, resulting in insufficient blood supply to the heart muscle. This leads to nutrient and oxygen deficiency in the myocardium, causing cardiac dysfunction. According to market research firm Technavio, the global myocardial infarction treatment market is expected to grow at an annual rate of 4.7% and reach $2.02 billion by 2026. Recently, research on myocardial infarction treatments using stem cell-derived nanovesicles such as exosomes to regulate inflammatory responses has been conducted; however, stem cells are difficult to mass-produce, limiting the economic feasibility of such treatments.

The research team confirmed the potential for treating severe myocardial infarction by reducing inflammatory responses in the heart muscle through nanomedicine derived from apoptotic cells undergoing biochemical changes within cells. This response was made possible by attaching peptides specific to ischemic myocardial infarction sites and substances specific to macrophage phagocytosis to the surface of fibroblasts. To this end, the team developed nanovesicles by inducing apoptosis in surface-modified fibroblasts that possess anti-inflammatory properties and can be specifically delivered to macrophages in the myocardial infarction area.

[Figure 1] The fabrication process of ApoNV-DC and its mechanism for treating myocardial infarction. Photo by KIST

In animal experiments, nanovesicles administered intravenously to rats were effectively delivered to the myocardial infarction site and were found to be specifically and abundantly taken up only by macrophages. As a result, the left ventricular ejection fraction (LVEF), an indicator of left ventricular contractility, increased by more than 1.5 times compared to the control group over four weeks, confirming an improvement in cardiac output. Additionally, inflammation was alleviated at the myocardial infarction site, fibrosis was reduced, and cardiac function improved with increased vascular preservation and myocardial cell survival.

Dr. Yoon-Ki Jeong stated, “This is the first study to apply nanovesicles produced from apoptotic cells to treat myocardial infarction, and because it uses normal cells rather than stem cells, it has the advantage of being mass-producible.” He added, “We plan to conduct further studies to verify the efficacy and safety of this treatment through clinical trials.”

The results of this study were published in the June issue of the international materials science journal Advanced Functional Materials (IF: 19.0, top 4.7% in JCR category).

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