Cytoskeletal mechanics in pressure-overload cardiac hypertrophy

Hirofumi Tagawa, Ning Wang, Takahiro Narishige, Donald E. Ingber, Michael R. Zile, George Cooper IV

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalCirculation Research
Volume80
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • cardiocyte
  • cytoskeleton
  • hypertrophy
  • microtubule

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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