| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309; 2 Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106; 3 Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710
Familial hypertrophic cardiomyopathy
(HCM) is an autosomal dominant disease characterized by varying degrees
of ventricular hypertrophy and myofibrillar disarray. Mutations in
cardiac contractile proteins cause HCM. However, there is an
unexplained wide variability in the clinical phenotype, and it is
likely that there are multiple contributing factors. Because
mitochondrial dysfunction has been described in heart disease, we
tested the hypothesis that mitochondrial dysfunction contributes to the
varying HCM phenotypes. Mitochondrial function was assessed in two
transgenic models of HCM: mice with a mutant myosin heavy chain gene
(MyHC) or with a mutant cardiac troponin T (R92Q) gene. Despite
mitochondrial ultrastructural abnormalities in both models, the rate of
state 3 respiration was significantly decreased only in the mutant MyHC
mice by ~23%. Notably, this decrease in state 3 respiration preceded
hemodynamic dysfunction. The maximum activity of 
-ketogutarate
dehydrogenase as assayed in isolated disrupted mitochondria was
decreased by 28% compared with isolated control mitochondria. In
addition, complexes I and IV were decreased in mutant MyHC transgenic
mice. Inhibition of 
-adrenergic receptor kinase, which is elevated in mutant MyHC mouse hearts, can prevent mitochondrial respiratory impairment in mutant MyHC mice. Thus our results suggest that mitochondria may contribute to the hemodynamic dysfunction seen in some
forms of HCM and offer a plausible mechanism responsible for some of
the heterogeneity of the disease phenotypes.
mitochondria; transgenic
This article has been cited by other articles:
|
|
 |
|
  K. Unno, S. Isobe, H. Izawa, X. W. Cheng, M. Kobayashi, A. Hirashiki, T. Yamada, K. Harada, S. Ohshima, A. Noda, et al. Relation of functional and morphological changes in mitochondria to myocardial contractile and relaxation reserves in asymptomatic to mildly symptomatic patients with hypertrophic cardiomyopathy Eur. Heart J., August 1, 2009; 30(15): 1853 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Watson, J. E. B. Reusch, S. A. McCune, L. A. Leinwand, S. W. Luckey, J. P. Konhilas, D. A. Brown, A. J. Chicco, G. C. Sparagna, C. S. Long, et al. Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H246 - H259. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ascensao, J. Magalhaes, J. M. C. Soares, R. Ferreira, M. J. Neuparth, F. Marques, P. J. Oliveira, and J. A. Duarte Moderate endurance training prevents doxorubicin-induced in vivo mitochondriopathy and reduces the development of cardiac apoptosis Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H722 - H731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Phillips, I. Drenjancevic-Peric, J. C. Frisbee, and J. H. Lombard Chronic AT1 receptor blockade alters mechanisms mediating responses to hypoxia in rat skeletal muscle resistance arteries Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H545 - H552. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
