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Pharmacological and genetic rescue of mitochondria to treat heart failure
Korea (KMSA) - Inje university, Busan
Cardiovascular and Metabolic Disease Center, College of Medicine
Jubert Marquize, Hyoung Kyu Kim, Dae Yun Seo, Nammi, Park, Jin Han
English or Korean
Type of Research Project
- Basic science
What is the background of the project?
Diabetes mellitus (DM) is a complicated metabolic disease with various complications, including diabetic cardiomyopathy (DCM), and is a risk factor for the development of heart failure. DCM is the major cause of mortality and morbidity in DM patients and is characterized by abnormal ventricle structure and function in diabetic patients without coronary artery disease or hypertension. Patients and animal models of DCM exhibit structural cardiac remodeling, such as ventricular hypertrophy and interstitial fibrosis, and functional impairments, including systolic and diastolic dysfunctions. Currently, there is no specific therapy for DCM patients in clinical practice despite the critical need. Increased oxidative stress, alterations of energy metabolism, and apoptotic cardiac cell death, resulting from mitochondrial dysfunction are implicated in the pathogenesis of DCM and present potential therapeutic targets. Studies in diabetic animal models have revealed impairments in state 3 mitochondrial oxygen consumption, respiratory chain complex activity, and mitochondrial ultrastructure and proliferation in the heart. Similarly, patients with type 2 DM show abnormal ATP generation, fatty acid utilization, and oxidative phosphorylation in cardiac mitochondria. Nevertheless, only a few studies have demonstrated a beneficial effect of mitochondrion-targeted antioxidant therapy in DCM.
What is the aim of the project?
The aims of present study were to study mitochondrial dysfunction involved in DCM and pharmacological and genetic rescue of mitochondria can restore cardiac function in late-stage DCM.
What techniques and methods are used?
1. Molecular biology with PCR, RT-PCR, real-time PCR, and sequencing 2. Fluorescence imaging with confocal microscope 3. Electrophysiology with patch-clamp techniques 4. In vivo cardiac function validation with echocardiography 5. Mitochondrial function assay: oxygen consumption 6. Animal model of exercise
What is the role of the student?
- The tasks will be done under supervision
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
The students will participate in the work-in-progress and the seminars. The student can get the basic concept of energy metabolism, mitochondrial physiology and cardiac physiology. He or she can participate as co-author in the experiment for mitochondrial energy metabolic derangements in heart failure (depending on his/her contribution) - he/she can be one of authors of original articles.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Yes, there are several theoretical teaching provided.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student’s name will be mentioned in a future publication - The student will have the opportunity to present the results together with the supervisor at a conference
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Basic skills and knowledge for physiological laboratory work.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields - Dental medicine students (IADS members)
- The students can find the related articles from PubMed by typing the words "mitochondria" and "heart failure".
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