Professor Kim Jong-min’s research team of Life Systems discovers a new method
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- Writer 커뮤니케이션팀
- 보도일자 2014-11-20
Kim Jong-min’s research team at our university's Life Systemsms conducted a joint international study with Professor Cheon Hyeong-jun’s research team at Yale University in the United States, and as a result, they have investigated the cause of pulmonary arterial hypertension and discovered a new compound for curing the disease. A breakthrough is expected in the development of medicine for this fatal disease, pulmonary arterial hypertension, which has a mortality rate of 45% within 3 years of diagnosis.
The findings of the study were introduced in the online edition of Circulation, an expert journal in the cardiovascular field, on October 21, and the printed version is planned to be published in late November. Circulation is an official expert journal of the American Heart Association (AHA) in the U.S. that boasts the world's highest authority in the cardiovascular field with 14.948 impact factor (IF/paper citation index).
(Link to Journal)
http://circ.ahajournals.org/content/early/2014/10/21/CIRCULATIONAHA.114.013339
According to the research team, pulmonary arterial hypertension is a disease that deforms blood vessels as pulmonary vascular cells abnormally increase and results in poor cardiovascular circulation due to an increase in pulmonary artery pressure. As a result, fatality occurs due to heart failure caused by overload, and it is a deadly disease that has a 45% mortality rate within 3 years of diagnosis. According to a survey, there are about 100 thousand patients worldwide diagnosed with the disease and about 2 thousand patients in Korea.
Medicines that have been developed up to now applied the strategy of reducing the resistance of blood flow by expanding the blocked or narrowed pulmonary arteries. However, when these medicines were administered to the patients, it only resulted in the relief or delay of the symptoms and the high mortality rate wasn’t diminished.
Accordingly, Professor Kim Jong-min’s research team decided to approach the problem from a different angle than the existing studies. They attempted to identify the cause of abnormal increase in the pulmonary vascular cells and propose a new treatment paradigm for suppressing that increase.
As a result, they've discovered that the expression of small microRNA is inhibited due to the inhibited activation of MEF2 transcription factor in the pulmonary arteries of pulmonary arterial hypertension patients and this is inducing abnormal increase of pulmonary vascular cells and deformation of blood vessels. Based on this newly identified pathogenesis of pulmonary arterial hypertension, a special compound (MC1568) has been discovered that can recover the inhibited microRNA to a normal level by reactivating MEF2 transcription factor which has been inhibited.
The research team demonstrated the improvement effect of MC1568 such as reduction in the pressure of pulmonary arteries and inhibition of increase of pulmonary vascular cells by administering MC1568 to a rat animal model with pulmonary hypertension through the abdominal cavity. The compound that has been proven to be effective is expected to be applied to patients with pulmonary arterial hypertension.
The results of this research were achieved through joint international cooperation with Professor Cheon Hyeong-jun’s research team, one of the top authorities in the field of pulmonary arterial hypertension at Yale University, and the research was supported by NRF's New Researcher Support Program and KHIDI's Translational Research Department. Professor Kim Jong-min said, "I believe this study is significant because a medicine of a new paradigm is proposed that can target microRNA which suppresses the abnormal increase of pulmonary vascular cells instead of existing medicines that target the expansion of blood vessels. With thorough examination of possible side effects from MC1568 by other institutions or organizations, despite the absence of side effects to the heart from MC1568 having been demonstrated through several investigations, I believe this will create a good opportunity to apply the medicine in human patients."
- Explanation of Keywords
microRNA : MicroRNA is known as a short single-stranded RNA of 19~25 nucleotides, which functions as a post-transcriptional regulator during the gene expression process.
Pulmonary arterial hypertension : A disease with symptoms such as shortness of breath, dizziness and loss of consciousness, due to an increase in pulmonary arterial pressure caused by various reasons (during normal state: above 25 mmHg pulmonary arterial pressure, during exercise: above 30mmHg)
MEF2 transcription factor : Myocyte Enhancer Factor-2 (MEF2) is known as an important transcription factor and protein that adjusts the expression of genes related to specialization and generation, and recently, it is known to be very important in maintaining the homeostasis of the pulmonary vascular system.