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Multiscale characterization of heart failure.
F Sahli Costabal1, J S Choy2, K L Sack3
1Departments of Mechanical Engineering & Bioengineering, Stanford University, CA, USA.
Acta Biomaterialia
|January 11, 2019
Summary
Increased sarcomere number drives myocyte lengthening, a key factor in dilated heart failure progression. This study links subcellular changes to organ-level cardiac dilation, suggesting new therapeutic targets.
Area of Science:
- Cardiovascular Biology
- Biophysics
- Computational Biology
Background:
- Dilated cardiomyopathy causes heart failure through contractile dysfunction.
- Mechanotransduction pathways increase sarcomere number, leading to myocyte lengthening and ventricular dilation.
- The precise link between sarcomere dynamics, myocyte morphology, and organ-level dilation is not fully understood.
Purpose of the Study:
- To quantify correlations between sarcomere dynamics, myocyte morphology, and ventricular dilation in dilated cardiomyopathy.
- To establish a multiscale understanding connecting subcellular changes to organ-level cardiac dysfunction.
Main Methods:
- A chronic eight-week volume overload animal study in pigs.
- Continuum growth modeling and Bayesian inference.
- Machine learning techniques to analyze data across scales.
Main Results:
- Sarcomere number increased by 3.8%/week, driving myocyte lengthening (3.3%/week).
- Myocyte lengthening explained 54% of cardiac dilation.
- Serial sarcomere number was the primary determinant of myocyte lengthening (88%).
Conclusions:
- Sarcomere number and myocyte length are closely correlated and are major determinants of dilated heart failure.
- Altering sarcomere turnover presents a potential therapeutic strategy for heart failure.
- This study provides a multiscale framework for understanding and potentially treating heart failure.
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