Research team, led by prof. Jin Won Kim from KU Guro hospital, develops target therapy for high-risk atherosclerotic plaques

The therapy maximizes therapeutic effects with a minimum of side effects

▲ Jah Yeon Choi, Ph.D. student, Korea University Medical School (left, first author) and Prof. Jin Won Kim, Cardiovascular Center, Korea University Guro Hospital (right, corresponding author)

Prof. Jin Won Kim from Cardiovascular Center, Korea University Guro Hospital developed a target therapy that selectively treats high-risk atherosclerotic plaque, which can cause myocardial infarction and heart failure.

Target therapy adopts technologies that selectively target specific cells or molecules, thereby minimizing side effects in treating diseases. The therapy can be rapidly developed as a result of the progress made in the field of nanotechnology. Nano-size drug delivery systems have a high affinity to the target and therefore, maximizes therapeutic effects with a minimum of side effects in the body. Despite remarkable advancements in oncology, the targetable strategy in cardiovascular diseases has rarely been explored.

This research paid attention to the fact that macrophages mediate plaque progression and ruptures. The research team developed a macrophage mannose receptor (MMR)-targeted biocompatible nanocarrier loaded with lobeglitazone (MMR-Lobe), which is able to activate PPARγ pathways specifically within inflamed high-risk plaques. The MMR-Lobe effectively reduced both plaque burden and inflammation without any meaningful side effects reported (Figure 1).

In particular, a new molecule imaging technique optimized to the artery of small animals was developed and its effect was proven with the use of an in vivo imaging system (Figure 1). How the targeted MMR-Lobe works was fully tracked and shown in Figure 2.

Prof. Kim said, “Despite the progress of modern medicine, cardiovascular diseases are still one of main causes of death,” stressing the significance of this research is that “MMR-Lobe can be an alternative to cardiovascular disease treatment.” He also added, “We are currently examining how to completely integrate this treatment and molecule image system, and this is expected to help develop a customized treatment with new diagnoses.”

As this research has been recognized as trailblazing in the field of target therapy in MMR nanocarriers, Jah Yeon Choi (first author) won “The Young Investigator Award by the Korean Society of Cardiology” last year. MMR-Lobe has acquired local and overseas patents, and the research team is working with a local pharmaceutical company in order to apply the technology in clinical tests.

This work was supported by the National Research Foundation of Korea and the Korean Ministry of Science and ICT. The findings were published in a recent issue of Theranostics.

Article Title: Therapeutic Effects of Targeted PPARɣ Activation on Inflamed High-Risk Plaques Assessed by Serial Optical Imaging In Vivo

[ Figure Description ]

Figure 1: Schematic illustration of MMR-Lobe and in-vivo microscopy image system of small animals, resulting in reduction of atherosclerotic plaques and inflammation activity after the target therapy

Figure 2: Schematic illustration of targeted MMR-Lobe effects

Circulating MMR-Lobe specifically binds to high-risk plaque macrophages in atherosclerotic plaques and releases lobeglitazone, thus resulting in reduction of inflammation activity and maximizing therapeutic effects.

[ Terminology ]

* Myocardial infarction: The irreversible damage that occurs when a coronary artery becomes blocked, which then leads to the formation of a blood clot

* High-risk atherosclerotic plaque: Caused by fatty deposits within arteries. These buildups can cause an artery wall to get thicker and narrow the opening. Most atherosclerotic plagues remain clinically silent short term. However, when inflammatory reaction occurs by the infiltration of specific cells, they can cause myocardial infarction or heart failure.

* Nanotechnology: A technology that synthesizes, assembles, controls, or measures materials as small as a billionth of a meter in size.

* Macrophages: Important cells of the immune system that engulf and destroy antigens. Macrophages that accumulate in atherosclerotic plaques engulf cholesterol and cholesterol-laden macrophages in the artery wall can cause inflammatory response, influencing atherosclerotic plaques.

* Macrophage mannose receptor (MMR): A transmembranal lectin primarily present on the surface of macrophages. Recent research findings have reported that MMRs are over expressed in high-risk atherosclerotic plaques.

* Lobeglitazone: An antidiabetic medication from the thiazolidinedione class of drugs. It functions as an insulin sensitizer by binding and activating (PPAR) gamma within fat cells, enhancing the release of cholesterols and reducing inflammation.

* In vivo image system: An microscopy image system that the research team developed in order to show the distribution of atherosclerotic plaques and the level of inflammation within the blood vessels of small animals.