7. REGULATORY MECHANISMS OF AGE-RELATED DIASTOLIC DYSFUNCTION

Department: Bioengineering
Faculty Advisor(s): Adam J Engler

Primary Student
Name: Gaurav Kaushik
Email: gkaushik@ucsd.edu
Phone: 858-246-1469
Grad Year: 2014

Abstract
Due to its short lifespan and genetic malleability, Drosophila melanogaster is a tractable system in which to study the effects of senescence and mutation on cardiac function. The bilayered Drosophila heart tube consists of a layer of cardiac myocytes bonded to a proto-skeletal ventral muscle layer. We have developed an atomic force microscopy-based micromechanical method to determine the stiffness of individual layers within a mechanically-heterogeneous sample, allowing for investigation of each muscle group in the Drosophila heart from a single indentation. Through optical and mechanical screening, we have found that aging phenotypes varies from strain to strain. Female yellow-white flies experience a significant decrease in diastolic diameter between 1 and 5 weeks of age (>20%) and micromechanical analysis revealed that their cardiomyocytes stiffen with age proximal to the intercalated discs (1.8 0.13 to 3.8 0.30 kPa). Conversely, another laboratory control strain, white 1118, is significantly more arrhythmic but experiences less diastolic dysfunction (<10% decrease in diastolic diameter) and was found to have no change in stiffness with age (p > 0.10). This analysis of the Drosophila heart tube represents the very first in situ indentation of living myocardium, preserving cell-cell and cell-matrix adhesions as seen in vivo, and has allowed us to resolve differences in passive cardiac mechanics on the submicron scale. DNA-microarrays have identified a host of mechanically-sensitive proteins to have significantly altered expression with age in yellow-white. Screening through RNA-interference targeted against promising mammalian-conserved candidates may reveal the molecular mechanisms of age-related myocardial stiffening and diastolic dysfunction that ultimately lead to heart failure.

« Back to Posters or Search Results