CYTOSKELETAL MECHANICS IN PRESSURE-OVERLOAD CARDIAC-HYPERTROPHY

We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormal ity intrinsic to the myofilament portion of the cardiocyte cytoskeleto n but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To deter mine how, in physical terms, this increased microtubule density mechan ically overloads the contractile apparatus at the cellular level, we m easured cytoskeletal stiffness and apparent viscosity in isolated card iocytes via magnetic twisting cytometry, a technique by which magnetic ally induced force is applied directly to the cytoskeleton through int egrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptid e. Measurements were made in two groups of cardiocytes from cats with right ventricular (RV) hypertrophy induced by pulmonary artery banding : (1) those from the pressure-overloaded RV and (2) those from the nor mally loaded same-animal control left ventricle (LV). Cytoskeletal sti ffness increased almost twofold, from 8.53+/-0.77 dyne/cm(2) in the no rmally loaded LV cardiocytes to 16.46+/-1.32 dyne/cm(2) in the hypertr ophied RV cardiocytes. Cytoskeletal apparent viscosity increased almos t fourfold, from 20.97+/-1.92 poise in the normally loaded LV cardiocy tes to 87.85+/-6.95 poise in the hypertrophied RV cardiocytes. In addi tion to these baseline data showing differing stiffness and, especiall y, apparent viscosity in the two groups of cardiocytes, microtubule de polymerization by colchicine was found to return both the stiffness an d the apparent viscosity of the pressure overload-hypertrophied RV cel ls fully to normal. Conversely, microtubule hyperpolymerization by tax ol increased the stiffness and apparent viscosity Values of normally l oaded LV cardiocytes to the abnormal values given above for pressure-h ypertrophied RV cardiocytes. Thus, increased microtubule density const itutes primarily a viscous load on the cardiocyte contractile apparatu s in pressure-overload cardiac hypertrophy.