Multi-Scale Modeling and Systems Mechanobiology of Ventricular Hypertrophy and Failure Event as iCalendar

(Seminars)

14 June 2016

4 - 5pm

Venue: Ground Floor

Location: Ground Floor Seminar Room (G10)

Host: 70 Symonds Street, Auckland Central.

A Bioengineering seminar by Prof. Andrew D. McCulloch, Distinguished Professor of Medicine and Bioengineering, University of California San Diego

Abstract

Ventricular hypertrophy and heart failure are multi-factorial, multi-scale problems in which altered whole body hemodynamics and neurohormonal factors lead to complex remodeling responses in the myocardium. We have developed multi-scale models of ventricular biomechanics and used them to elucidate the early defects in myocardial mechanics that may promote adverse remodeling and failure in gene-targeted mouse models of hypertrophic and dilated cardiomyopathy. Models of mechanically-regulated myocyte growth and remodeling suggest that a growth law in which myocytes respond differentially to transverse and longitudinal strains can explain differences between ventricular hypertrophy associated with normal postnatal growth, aortic stenosis, mitral valve regurgitation and asymmetric electrical activation. In-vitro studies in micropatterned neonatal mouse ventricular myocytes subjected to anisotropic biaxial stretch show differences in transcriptional responses when the major axis of stretch is longitudinal compared with transverse to the myofilament axis. We introduce a network model of myocyte mechanical signaling and regulation of gene expression and use it to identify pathways associated with loading that is transverse or parallel to the myofilament axis. Finally, we illustrate the application of these modeling approaches to the clinical problem of cardiac resynchronization for dyssynchronous heart failure.

Supported by NIH grants 8 P41 GM103426-19, P50 GM094503-01A1, 1R01HL105242-01