Molecular
Heart failure

Molecular Heart failure
清水 逸平

Department of Cardiovascular Biology and Medicine,
Juntendo University Graduate School of Medicine

Associate ProfessorIppei Shimizu

To establish preemptive medicine for age-related disorders including heart failure.

Patients with heart failure are increasing rapidly, and “heart failure pandemic” has become a global issue worldwide. Mechanisms of heart failure are complex, do not allow a simple approach, and many unmet medical needs exist to be explored. Our group is trying to develop next generation therapies for this critical condition by establishing a new concept and hypotheses tested with series of basic/translational/clinical studies.

(Please visit the following for more details. https://www.mol-aging.com/)

Inspiration received through encountering great mentors, colleagues and friends

Living abroad for nearly 10 years in my life, I had opportunities to encounter new culture, custom, language, friends, scenery since my childhood. Through these experiences, I became flexible, social and also oriented to have my own identity through out-of-the-box thinking. At the university, I met several mentors with highest regards, and decided to become a cardiologist after graduation. Cardiovascular treatment is extremely dynamic, and on top of this, basic/translational/clinical research is active all around the world. Many unmet medical needs underly in heart failure, therefore I set one of my research goals to generate new therapies for this challenging disorder.
Japan has become a super-aging society and patients with heart failure are increasing rapidly.
Heart failure diminishes quality of life, reduces daily activities and enhances frailty, and is urgent to develop new therapies.

Heart failure is a systemic disease

There are two types of heart failure. Heart failure with reduced ejection fraction (HFrEF) is characterized with reduction in systolic function of left ventricle, and heart failure with preserved ejection fraction (HFpEF) develops through reduction in diastolic function with preserved systolic function. Several drugs are generated to combat HFrEF, however, therapies for HFpEF are extremely limited. Heart failure can be caused by variety of factors affecting cardiac tissue as well as systemic organs. Organ-organ interactions exist and are crucial to understand mechanisms involved in pathologies of failing heart. Indeed, heart failure is a systemic disease, and we have so far elucidated the role of metabolic dysfunction and aging signaling in this disorder. For example, previously we published a paper demonstrating the link between systemic insulin resistance (hyperinslunemia) and heart failure. We found excessive cardiac insulin signaling promotes heart failure, and now it is widely accepted that diabetic drugs mediating their biological effects without enhancing insulin signaling should initially be used to reduce risk of heart failure. Aging links with comorbidities including hypertension, diabetes, obesity and atherosclerotic diseases. Together with these risk factors, aging per se is considered to promote pathogenesis in with heart failure. Aging also develops in cellular level, and we previously showed cell senescence becomes pathogenic in heart failure, and the question is how we can generate therapies targeting aging or age-related signaling.

Proposing a new concept of age- related diseases

Current medical science recognizes HFpEF, atrial fibrillation, chronic kidney disease (CKD), and non-alcoholic steatohepatitis (NASH) as different diseases. Common pathogenesis is fibrosis-induced organ dysfunction that develop with aging. Therefore, recently I defined them comprehensively with a new concept described " Age-related Fibrotic Disorder (A-FiD)", and won an award from the National Academy of Medicine, USA in October 2020. With collaborators, I am trying to set up a research consortium with more than 50 global members from Japan and overseas, enabling us to do comprehensive and conclusive basic/translational/clinical research. It is considered that there are more than 13 million patients with HFpEF worldwide, about 30 million patients of atrial fibrillation, 3-5% of the world population is having NASH, and 10-12% of the world population is suffering from CKD. Working with A-FiD research consortium members, I believe we can establish new therapies for these diseases.
Keywords of our research topics are “sync-aging”, “senometabolite”, “senoprotein”, “senolytics”, “etabolic dysfuction” targeting age-related diseases such as heart failure, atrial fibrillation, atherosclerotic diseases, obesity, diabetes, NASH, CKD etc. Please feel free to contact us if you are interested in joining Ph.D. program.

清水 逸平
Ippei Shimizu

2002 Chiba University, School of Medicine.
Visit the following site for more details.
https://www.mol-aging.com/