17. VINCULIN CONTRIBUTES TO THE PASSIVE STIFFNESS OF MYOCARDIUM

Department: Bioengineering
Faculty Advisor(s): Jeffrey H. Omens | Andrew McCulloch

Primary Student
Name: Joyce Shaw-An Chuang
Email: jschuang@ucsd.edu
Phone: 858-373-8966
Grad Year: 2010

Abstract
In cardiomyocytes, the costamere links the Z disc to the surrounding extracellular matrix. Proteins at these junctions include integrins, talin, and vinculin (Vin). Vin is also found in the intercalated discs. Cardiac-specific Vin knockout (VinKO) mice have a sudden death phenotype early in life (<12 weeks of age) with a progressive dilated cardiomyopathy leading to 100% mortality by 32 wks. At 7 weeks of age, systolic ventricular function is normal. We hypothesize that deletion of the costameric protein Vin leads to changes in passive stiffness prior to the onset of systolic dysfunction. Vin deletion may disrupt the normal force transmission pathways from ECM to cytoskeleton through the integrin-based costamere or cell-to-cell force transmission along the myocyte axis, which may manifest in altered passive material properties of the myocardium. To test the mechanical properties of myocardial tissue, a system was developed in which murine right ventricular papillary muscles could be passively strained in the axial direction while simultaneously measuring force. Papillary muscles from 7 week old VinKO mice and WT controls were isolated and stretched. Stress-strain analysis was used to measure passive stiffness in the direction of myocardial fibers. Stress-strain curves were significantly different between WT and VinKO papillary muscles (p<0.05). The slope of the VinKO curve was less than in the WT curve, indicating that VinKO muscles are more compliant in the fiber direction. This data suggests that Vin contributes to the passive mechanical properties of the myocardium, and disrupting the mechanical linkage between the cytoskeleton and the cell membrane reduces the overall stiffness of the myocardium.

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