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Heart Failure Pathogenesis Elucidation and New Treatment Method Development
Mikako Katagiri1, Shintaro Yamada1, Manami Katoh1,2
1Department of Cardiovascular Medicine, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
Insights
Heart failure (HF) is a growing global concern. New research highlights ischemia and DNA damage as key factors in HF progression, crucial for developing precision medicine.
Area of Science:
- Cardiology
- Molecular Biology
- Pathophysiology
Background:
- Heart failure (HF) is a major cause of death globally, with Japan experiencing an "HF pandemic" due to an aging population.
- HF represents the advanced stage of cardiovascular diseases like valvular heart disease, ischemic heart disease, atrial fibrillation, and hypertension.
- Cardiac hypertrophy, initially a compensatory mechanism for increased workload, can lead to HF if continuous stress thins the cardiac walls.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the progression from cardiac hypertrophy to heart failure.
- To introduce novel insights into HF pathophysiology derived from basic research.
- To facilitate the development of precision medicine for heart failure.
Main Methods:
- Review of basic research findings on cardiac hypertrophy and heart failure.
- Analysis of molecular mechanisms, including ischemia and DNA damage, in HF progression.
- Examination of genetic mutations linked to cardiomyopathy and HF prognosis.
Main Results:
- Ischemia and DNA damage were identified as significant contributors to the progression of hypertrophy to heart failure.
- Genetic mutations influencing cardiomyopathy and patient prognosis have been identified.
- New molecular paradigms for understanding HF pathophysiology have been uncovered.
Conclusions:
- Understanding the molecular basis of HF is critical for advancing treatment strategies.
- Basic research provides essential insights into the complex pathophysiology of heart failure.
- Elucidating these mechanisms is key to realizing precision medicine for HF patients.
Abstract:
Heart failure (HF) is a leading cause of death worldwide. In Japan, the number of HF patients has increased with its aging population, resulting in "HF pandemic." HF is the final stage of various cardiovascular diseases, including valvular heart disease, ischemic heart disease, atrial fibrillation, and hypertension. Cardiac hypertrophy is a compensatory response to increased workload and maintains cardiac function. Pressure overload due to mechanical stress causes cardiac hypertrophy, whereas continuous cardiac stress reduces wall thickness and consequently causes HF. Understanding the molecular mechanisms underlying this process is crucial to elucidate HF pathophysiology. We demonstrated that ischemia and DNA damage are important in the progression of hypertrophy to HF. Genetic mutations associated with cardiomyopathy and prognosis has been identified. To realize precision medicines for HF, the underlying molecular mechanisms need to be elucidated. In this review, we introduce new paradigms for understanding HF pathophysiology discovered through basic research.
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