| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Kinesiology and Applied Physiology, 2 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0354; and 3 Cardiology Division, University of Colorado Health Sciences Center, Denver, Colorado 80262
Mutations in the cardiac myosin heavy chain
(MHC) can cause familial hypertrophic cardiomyopathy (FHC). A
transgenic mouse model has been developed in which a missense (R403Q)
allele and an actin-binding deletion in the 
-MHC are expressed in
the heart. We used an isovolumic left heart preparation to study the
contractile characteristics of hearts from transgenic (TG) mice and
their wild-type (WT) littermates. Both male and female TG mice
developed left ventricular (LV) hypertrophy at 4 mo of age. LV
hypertrophy was accompanied by LV diastolic dysfunction, but LV
systolic function was normal and supranormal in the young TG females
and males, respectively. At 10 mo of age, the females continued to
present with LV concentric hypertrophy, whereas the males began to
display LV dilation. In female TG mice at 10 mo of age, impaired LV
diastolic function persisted without evidence of systolic dysfunction.
In contrast, in 10-mo-old male TG mice, LV diastolic function worsened and systolic performance was impaired. Diminished coronary flow was
observed in both 10-mo-old TG groups. These types of changes may
contribute to the functional decompensation typically seen in
hypertrophic cardiomyopathy. Collectively, these results further underscore the potential utility of this transgenic mouse model in
elucidating pathogenesis of FHC.
myosin; isovolumic; diastolic; systolic
This article has been cited by other articles:
|
|
 |
|
  P Elliott and P Spirito Prevention of hypertrophic cardiomyopathy-related deaths: theory and practice Heart, October 1, 2008; 94(10): 1269 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Palmer, Y. Wang, P. Teekakirikul, J. T. Hinson, D. Fatkin, S. Strouse, P. VanBuren, C. E. Seidman, J. G. Seidman, and D. W. Maughan Myofilament mechanical performance is enhanced by R403Q myosin in mouse myocardium independent of sex Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1939 - H1947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Md. S. Bhuiyan, N. Shioda, and K. Fukunaga Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1606 - E1614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Murphy and C. Steenbergen Gender-based differences in mechanisms of protection in myocardial ischemia-reperfusion injury Cardiovasc Res, August 1, 2007; 75(3): 478 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Mendelsohn and R. H. Karas Molecular and Cellular Basis of Cardiovascular Gender Differences Science, June 10, 2005; 308(5728): 1583 - 1587. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Skavdahl, C. Steenbergen, J. Clark, P. Myers, T. Demianenko, L. Mao, H. A. Rockman, K. S. Korach, and E. Murphy Estrogen receptor-{beta} mediates male-female differences in the development of pressure overload hypertrophy Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H469 - H476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Arimura, A. Helbling-Leclerc, C. Massart, S. Varnous, F. Niel, E. Lacene, Y. Fromes, M. Toussaint, A.-M. Mura, D. I. Keller, et al. Mouse model carrying H222P-Lmna mutation develops muscular dystrophy and dilated cardiomyopathy similar to human striated muscle laminopathies Hum. Mol. Genet., January 1, 2005; 14(1): 155 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. H. Maass, K. Ikeda, S. Oberdorf-Maass, S. K.G. Maier, and L. A. Leinwand Hypertrophy, Fibrosis, and Sudden Cardiac Death in Response to Pathological Stimuli in Mice With Mutations in Cardiac Troponin T Circulation, October 12, 2004; 110(15): 2102 - 2109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-J. Du Gender modulates cardiac phenotype development in genetically modified mice Cardiovasc Res, August 15, 2004; 63(3): 510 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Palmer, D. E. Fishbaugher, J. P. Schmitt, Y. Wang, N. R. Alpert, C. E. Seidman, J. G. Seidman, P. VanBuren, and D. W. Maughan Differential cross-bridge kinetics of FHC myosin mutations R403Q and R453C in heterozygous mouse myocardium Am J Physiol Heart Circ Physiol, July 1, 2004; 287(1): H91 - H99. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Olsson, B. M. Palmer, B. L. Stauffer, L. A. Leinwand, and R. L. Moore Morphological and Functional Alterations in Ventricular Myocytes From Male Transgenic Mice With Hypertrophic Cardiomyopathy Circ. Res., February 6, 2004; 94(2): 201 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Petersen, J. Choy, B. Stauffer, F. Moien-Afshari, C. Aalkjaer, L. Leinwand, B. M. McManus, and I. Laher Coronary artery myogenic response in a genetic model of hypertrophic cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2244 - H2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Arad, J.G. Seidman, and C. E. Seidman Phenotypic diversity in hypertrophic cardiomyopathy Hum. Mol. Genet., October 1, 2002; 11(20): 2499 - 2506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. MAASS, J.P. KONHILAS, B.L. STAUFFER, and L.A. LEINWAND From Sarcomeric Mutations to Heart Disease: Understanding Familial Hypertrophic Cardiomyopathy Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 409 - 416. [Abstract] [PDF]
|
|
|
|
|
|
J. M. Nerbonne, C. G. Nichols, T. L. Schwarz, and D. Escande Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here? Circ. Res., November 23, 2001; 89(11): 944 - 956. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
