Role of microtubules versus myosin heavy chain isoforms in contractile dysfunction of hypertrophied murine cardiocytes.
In large mammals there is a correlation between microtubule network densification and contractile dysfunction in severe pressure-overload hypertrophy. In small mammals there is a similar correlation for the shift to beta-myosin heavy chain (MHC), a MHC isoform having a slower ATPase Vmax. In this study, murine left ventricular (LV) pressure overload invoked both mechanisms: microtubule network densification and beta-MHC expression. Cardiac beta-MHC was also augmented without altering tubulin levels by two load-independent means, chemical thyroidectomy and transgenesis. In hypertrophy, contractile function of the LV and its cardiocytes decreased proportionally; microtubule depolymerization restored normal cellular contraction. In hypothyroid mice having a complete shift from alpha-MHC to beta-MHC, contractile function of the LV and its cardiocytes also decreased, but microtubule depolymerization had no effect on cellular contraction. In transgenic mice having a cardiac beta-MHC increase similar to that in hypertrophy, contractile function of the LV and its cardiocytes was normal, and microtubule depolymerization had no effect. Thus, although both mechanisms may cause contractile dysfunction, for the extent of MHC isoform switching seen even in severe murine LV pressure-overload hypertrophy, microtubule network densification appears to have the more important role.
Gazes Cardiac Research Institute, Cardiology Division, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403, USA.
Yuji
Y
Ishibashi
Masaru
M
Takahashi
Yukihisa
Y
Isomatsu
Fei
F
Qiao
Yoshihiro
Y
Iijima
Hirokazu
H
Shiraishi
Janet M
JM
Simsic
Catalin F
CF
Baicu
Jeffrey
J
Robbins
Michael R
MR
Zile
George
G
Cooper
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007536:Isomerism; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012518:Sarcomeres / Q000502:physiology; D014404:Tubulin / Q000378:metabolism; D016474:Weight-Bearing
D014404:Tubulin; D018995:Myosin Heavy Chains; D002118:Calcium