© 1997 American Heart Association, Inc.
Articles |
Cytoskeletal Mechanics in Pressure-Overload Cardiac Hypertrophy
the Cardiology Section of the Department of Medicine and the Department of Physiology, Gazes Cardiac Research Institute, Medical University of South Carolina, and the Veterans Administration Medical Center (H.T., T.N., M.R.Z, G.C. IV), Charleston, SC; the Physiology Program (N.W.), Harvard School of Public Health, Boston, Mass; and the Departments of Surgery and Pathology (D.E.I.), Children's Hospital and Harvard Medical School, Boston, Mass.
We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the cardiocyte cytoskeleton. To determine how, in physical terms, this increased microtubule density mechanically overloads the contractile apparatus at the cellular level, we measured cytoskeletal stiffness and apparent viscosity in isolated cardiocytes via magnetic twisting cytometry, a technique by which magnetically induced force is applied directly to the cytoskeleton through integrin-coupled ferromagnetic beads coated with Arg-Gly-Asp (RGD) peptide. 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 normally loaded same-animal control left ventricle (LV). Cytoskeletal stiffness increased almost twofold, from 8.53±0.77 dyne/cm2 in the normally loaded LV cardiocytes to 16.46±1.32 dyne/cm2 in the hypertrophied RV cardiocytes. Cytoskeletal apparent viscosity increased almost fourfold, from 20.97±1.92 poise in the normally loaded LV cardiocytes to 87.85±6.95 poise in the hypertrophied RV cardiocytes. In addition to these baseline data showing differing stiffness and, especially, apparent viscosity in the two groups of cardiocytes, microtubule depolymerization by colchicine was found to return both the stiffness and the apparent viscosity of the pressure overload–hypertrophied RV cells fully to normal. Conversely, microtubule hyperpolymerization by taxol increased the stiffness and apparent viscosity values of normally loaded LV cardiocytes to the abnormal values given above for pressure-hypertrophied RV cardiocytes. Thus, increased microtubule density constitutes primarily a viscous load on the cardiocyte contractile apparatus in pressure-overload cardiac hypertrophy.
Key Words: hypertrophy • cardiocyte • cytoskeleton • microtubule
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