Skip Navigation

Cardiovascular Research 2001 50(3):509-515; doi:10.1016/S0008-6363(01)00205-X
© 2001 by European Society of Cardiology
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kamogawa, Y.
Right arrow Articles by Tei, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kamogawa, Y.
Right arrow Articles by Tei, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2001, European Society of Cardiology

Dystrophin-deficient myocardium is vulnerable to pressure overload in vivo

Yasuyuki Kamogawaa, Sadatoshi Biroa,*, Masato Maedaa, Manabu Setoguchia, Tatsumi Hirakawaa, Hiroki Yoshidab and Chuwa Teia

aFirst Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan
bDepartment of Pathology, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 8908520, Japan

* Corresponding author. Tel.: +81-99-275-5318; fax: +81-99-265-8447 biro{at}m2.kufm.kagoshima-u.ac.jp

Received 6 July 2000; accepted 2 January 2001


   Abstract
Top
 Abstract
1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 
Objective: Dystrophin provides mechanical reinforcement to the membranes of myocytes. Dystrophin abnormalities are known to cause cardiomyopathy and skeletal muscle disorders; however, the pathogenesis of these abnormalities remains unclear. Dystrophin-deficient skeletal muscle is vulnerable to stresses such as stretch and hypo-osmotic shock. We investigated whether the myocardium of dystrophin-deficient (mdx) mice shows increased vulnerability to acute pressure overload in vivo. Methods and results: Abdominal aortic banding was performed in 12-week-old mdx and control mice. The aortic pressure was measured by cannulation of the right carotid artery at the time of sacrifice. Systolic pressures in mdx mice at 0, 1, 2, 7 and 14 days after aortic banding were 100±11, 119±7, 123±4, 134±11 and 130±10 mmHg, respectively. Microscopic analysis revealed focal lesions in the left ventricular wall in banded mdx mice. These lesions consisted of damaged myocytes and inflammatory cells, and also of fibrosis at a late stage. Similar lesions were not observed in non-banded or banded control mice. The proportion of areas of lesions to total left ventricular area increased over time: 1.0±0.6% in mdx mice without aortic banding (sham, n=6), and 1.7±1.4% 1 day (n=6, vs. sham, NS), 2.6±1.9% 2 days (n=7, vs. sham, P<0.05), 6.3±6.5% 7 days (n=13, vs. sham, P<0.05) and 9.9±8.3% 14 days after aortic banding (n=15, vs. sham, P<0.01). Furthermore, linear regression analysis revealed a significant correlation between percentage of lesion area and systolic pressure in mdx mice (P<0.05). Conclusion: Dystrophin-deficient myocardium is more vulnerable than normal myocardium to pressure overload in vivo. This result has two clinical implications: (1) the patients with dystrophynopathy, such as the Duchenne and the Becker types of muscular dystrophy and X-linked type of dilated cardiomyopathy, who develop arterial hypertension should be treated aggressively, and (2) they should avoid stresses that elevate blood pressure.

KEYWORDS Blood pressure; Cardiomyopathy; Histo(patho)logy; Hypertension; Myocytes


   1 Introduction
Top
 Abstract
 1 Introduction
2 Methods
 3 Results
 4 Discussion
 References
 
Dystrophin is an important cytoskeletal component of striated muscle cells, in which it provides structural support to the plasma membranes [1–4]. Although the functional role of dystrophin is not completely understood, immunohistochemical analysis has demonstrated that this protein is localized in the sarcolemma [5]. Genetically transmitted abnormalities in the expression of this protein are complex and result in three clinically distinct disorders: the Duchenne (DMD) and the Becker (BMD) types of muscular dystrophy [6,7] and X-linked type of dilated cardiomyopathy [8].

The main role of the cytoskeleton is to provide the major structural framework to maintain cellular integrity. Dystrophin is thought to link between the subsarcolemmal cytoskeleton and the extracellular matrix. The N-terminal domain of dystrophin binds to F-actin in the cytoskeleton [9], whereas the C-terminal region interacts with a set of transmembrane- and membrane-associated proteins, including {alpha}, β-dystroglycans, {alpha}, β, {gamma}, {delta}-sarcoglycans, syntrophins, sarcospan and dystrobrevin [10–19]. {alpha}-Dystroglycan binds to laminin-2 (merosin) in the overlying basal lamina [11,15]. The findings that abnormalities in dystrophin [1,2,6–8], actin [20], merosin [21], and some of the dystrophin–glycoprotein complex [22–25] are linked to skeletal and/or cardiac muscle dystrophy in humans and in animal models, points to the importance of the appropriate transfer of extracellular stimuli to the interior of the cell to maintain sarcolemmal membrane stability. This concept is in accord with the observation that the lack of integrin {alpha}-7, which also transduces the extracellular signal to the interior of the cells via focal adhesion kinase, causes muscular dystrophy in mice [26].

Damage to both cardiac and skeletal muscle occurs in the majority of patients with DMD and BMD [25]. Furthermore, several studies have demonstrated that dystrophin-defected skeletal muscle cells are abnormally vulnerable to stretch [27,28] and hypoosmolarity [29,30]. However, no information is available on the susceptibility of dystrophin-deficient cardiac muscle to the damage induced by mechanical forces related to pressure overload. Accordingly, the present study was designed to compare the extent of cardiac damage following aortic banding in dystrophin-deficient and control mice.


   2 Methods
Top
 Abstract
 1 Introduction
 2 Methods
3 Results
 4 Discussion
 References
 
2.1 Animals and surgical procedure
Twelve-week-old male dystrophin-deficient (mdx) mice and control (C57BL/10ScSn) mice were anesthetized with sodium pentobarbital (50 mg/kg, i.p.) and diethylether. The aorta was exposed via a midline abdominal incision under a dissecting microscope. The abdominal aorta was banded with 6-0 silk thread between the right and left renal arteries using a 26-gauge needle (outside diameter, 0.45 mm) to standardize the diameter of the ligation [31,32]. Sham operation was performed in controls using an identical procedure, except for the ligation. This study was carried out in accordance with the Guide for Animal Experimentation, Faculty of Medicine, Kagoshima University and conforms with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996).

2.2 Measurement of aortic pressure
At 1, 2, 7, and 14 days after aortic banding, the right carotid artery was cannulated with a flame-stretched polyethylene tube (SP45; Natume, Tokyo, Japan) and connected to a polygraph system (Nihon Kohden, Tokyo, Japan) for measurement of the aortic pressure.

2.3 Microscopic analysis
After measurement of the aortic pressure, each mouse was sacrificed, the heart was excised and the atria removed. The ventricles were divided into the left ventricle, including the intraventricular septum, and right ventricular free wall. They were rinsed with HEPES buffer, weighed, fixed in neutral-buffered 10% formalin and embedded in paraffin. The tissue sections were stained with hematoxylin–eosin and Azan. Left ventricular hypertrophy was assessed by measurements of: (1) the ratio of left ventricular wet weight to body weight, and (2) the diameters of the myocytes (n=1000) in the area of the nucleus. To determine the degree of myocardial damage, three cross-sectional cuts of the left ventricle (apex, mid and basal portion) were selected and stained with Azan, and the percentage of the sum of the areas of lesion to the total area of the tissue was calculated using a computerized digital image analysis system (NIH image, NIH Research Serviced Branch) by two blinded observers. Three measurements were averaged.

2.4 Statistical analysis
All values are expressed as mean±S.D. Statistical comparison of aortic banded mice with sham-operated mice was performed with the Student's t-test for unpaired values. Linear regression analysis was performed to assess a correlation between aortic pressure and percentage of lesion area. P values <0.05 were considered statistically significant.


   3 Results
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
4 Discussion
 References
 
3.1 Mortality
The acute operative mortality was <20%, with the mortality for the mice that recovered from anesthesia being <10%. No significant difference in mortality existed between control and mdx mice.

3.2 Aortic pressure and left ventricular hypertrophy
Aortic pressure increased significantly 24 h after abdominal aortic banding in both control and mdx mice, but was not significantly different between the two groups (Fig. 1). Left ventricular hypertrophy was observed in the both groups at 14 days after aortic banding. The left ventricular weight to body weight ratio and the mean myocyte diameter in the area of the nucleus were significantly increased. There was no significant difference in the degree of the ventricular hypertrophy between in mdx and in control (Table 1).


Figure 1
View larger version (22K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Graph shows the time course of systolic pressure after abdominal aortic banding in control and mdx mice. ({square}) Sham-operated control mice on day 0 (n=5), 1 (n=6), 2 (n=7), 7 (n=9) and 14 (n=9); ({blacksquare}) aortic banded control mice on day 0 (n=5), 1 (n=6), 2 (n=19), 7 (n=10) and 14 (n=13); ({circ}) sham-operated mdx mice on day 0 (n=6), 1 (n=5), 2 (n=12), 7 (n=7) and 14 (n=11); (bullet) aortic banded mdx mice on day 0 (n=6), 1 (n=6), 2 (n=7), 7 (n=16) and 14 (n=15). *P<0.001 vs. sham.

 

View this table:
[in this window]
[in a new window]

  		Table 1 Hemodynamic and hypertrophic parameters in control and mdx micea

 
3.3 Histopathology
Microscopic observation revealed no myocyte damage, inflammatory cell infiltration or fibrosis in control mice with or without aortic banding. Lesions were scarcely found in sham-operated mdx mice (Fig. 2A–C). In mdx mice subjected to aortic banding, scattered focal lesions were observed (Fig. 2D). These lesions were present throughout the left ventricular wall (arrowheads), namely no damage-prone region was observed. These lesions consisted of injured cardiomyocytes characterized by disappearance of muscle fiber, mononuclear inflammatory cells (Fig. 2D–F), and also fibrosis, increase of collagen fibers assessed by Azan stain, at a late stage (Fig. 2G–I). In some banded mdx mice with many lesions, enlargement of left ventricle was observed (Fig. 2G). Mild interstitial fibrosis was observed at a late stage in control mice subjected to aortic banding (Fig. 2J–L). The percentage of lesion area to the total left ventricular area in mdx mice subjected to aortic banding increased significantly in a time-dependent manner (Fig. 3).


Figure 2
View larger version (155K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Representative light micrographs of left ventricles from the sham operated mdx mice (A), aortic banded mdx mice on day 2 (D) and on day 14 (G), and aortic banded control mice on day 14 (J). B and C, E and F, H and I, and K and L are light micrographs of the areas surrounded by arrows in A, D, G, and J, respectively, at higher magnification. Arrowheads show lesions. Scale bar in J represents 0.4 mm and in K and L 20 µm. HE, hematoxylin–eosin stain; Azan, Azan stain.

 

Figure 3
View larger version (17K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 The percentage of lesion area to the total left ventricular area in mdx mice subjected to abdominal aortic banding or sham operated mdx mice. ({square}) Sham-operated mdx mice on day 0 (n=6), 1 (n=5), 2 (n=6), 7 (n=7) and 14 (n=11); ({blacksquare}) aortic banded mdx mice on day 0 (n=6), 1 (n=6), 2 (n=7), 7 (n=13) and 14 (n=15). *P<0.05 vs. sham.

 
3.4 Pressure and lesion area
The localization and extent of lesion varied considerably from animal to animal. Therefore, we investigated a correlation between aortic pressure and lesion area. Linear regression analysis revealed a significant correlation between systolic pressure and the percentage of lesion area in mdx mice 14 days after aortic banding or sham operation (Fig. 4).


Figure 4
View larger version (19K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 Linear regression analysis showed a significant correlation between the percentage of lesion area and systolic pressure in mdx mice 14 days after aortic banding or sham operation. Y=0.365X–36.807, {gamma}2=0.422 (P<0.05).

 

   4 Discussion
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
References
 
The present study demonstrates that the dystrophin-deficient myocardium of mdx mice is more vulnerable than normal myocardium to pressure overload in vivo and that the degree of injury correlates with the level of systolic pressure. These findings are in accord with the concept that dystrophin provides mechanical reinforcement to the sarcolemmal membrane of cardiac myocytes.

Several studies have demonstrated the weakness of dystrophin-deficient muscle. Menke and Jockusuch [29,30] have noted decreased osmotic stability of dystrophin-deficient muscles from both mdx mice and DMD patients in vitro. Petrof et al. [27] and Moens et al. [28] have reported that skeletal muscle from mdx mice is damaged by contractions with stretch in vitro to a greater extent than is muscle from control mice. Carter et al. [33] and Vilquin et al. [34] have demonstrated that excessive running exercise leads to muscle damage in mdx mice. Furthermore, myotubes cultured from mdx mice show an increased susceptibility to oxidative stress induced by reactive oxygen species [35]. Injection of purified mast cell granules into the gastrocnemius muscle induced widespread myofiber necrosis in mdx mice [36], and triiodothyronine (T3) treatment induced more damage in both cardiac and skeletal muscles in mdx mice than in control mice [37]. These data and the observations in the present study suggest that dystrophin protects the muscle cells against the membrane damage induced by several stresses, especially by mechanical stress.

The present study is the first to describe the increased vulnerability of dystrophin-deficient cardiac myocytes in vivo to increased aortic pressure. We were unable to clarify the mechanism which renders dystrophin-deficient myocardium vulnerable to pressure overload in vivo. However, plausible mechanisms have been proposed. Intracellular Ca2+ has been reported to be elevated in skeletal muscle from mdx mice, and this change is associated with a high rate of protein degradation [38]. In addition, electrophysiologic studies have revealed that the open probability of Ca2+ leak channels is markedly increased in dystrophic myotubes [39], and that myotubes lacking dystrophin possess a novel type of mechano-transducing channel [40]. These may contribute to the elevation of the intracellular levels of Ca2+ in muscle of mdx mice and patients with DMD. Another possibility is induction of apoptosis in cardiomyocytes. Gottlieb et al. [41] first reported that cardiomyocytes underwent apoptosis after reperfusion injury. Then, apoptotic cardiomyocytes were found in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction, myocarditis, and arrythmias [42]. In addition, it is reported that apoptosis is induced in cardiomyocytes of pressure overload rats [43] and that apoptotic cells are found in dystrophin-deficient skeletal muscle [44]. We recently found that cultured dystrophin-deficient cardiac myocytes are prone to undergo apoptosis when they are stretched [45]. Additionally, Coral-Vazquez et al. [46] reported a novel mechanism for cardiomyopathy. In delta-sarcoglycan knockout mice, the disruption of the sarcoglycan sarcospan complex is found in vascular smooth muscle. This induces vascular dysfunction (e.g. coronary arteries), resulting in cardiomyopathy. Furthermore, Gnecchi-Ruscone et al. [47] reported that coronary vasodilator reserve, assessed by positron emission tomography, is significantly blunted in DMD and sarcoglycan-deficient limb-girdle muscular dystrophies patients compared with age-matched controls. Since the localization and extent of lesions in delta-sarcoglycan knockout mice [46] is similar to those in our study, it is possible that pressure overload induced cardiac lesions may be due to coronary vascular dysfunction. Further examination will be needed.

In the present study we have utilized dystrophin-deficient (mdx) mice, which have genotypic abnormalities identical to those in patients with DMD. These abnormalities involve a nonsense mutation in the dystrophin gene [48] and results in the absence of the dystrophin polypeptide. mdx mice show histologic signs of muscular dystrophy during the first 6 weeks of life [49]; however, their subsequent clinical course differs markedly from that of patients with DMD. The mdx mice show little weakness in skeletal or cardiac muscle, and have an almost normal life span. On histologic examination, cardiac muscle from mdx mice reveals few lesions at 8 weeks of age. Nevertheless, some small lesions are present after 9 weeks (unpublished data). One possible explanation for the clinical differences between mdx mice and DMD patients is that structurally related proteins compensate for the lack of dystrophin more effectively in mdx mice than in DMD patients. Utrophin, a dystrophin-related protein, is upregulated in mdx mice [50], and expression of this protein has been shown to attenuate the dystrophic changes in these animals. Mice lacking both dystrophin and utrophin develop skeletal and cardiac myopathies [51]. Even mdx mice developed a cardiomyopathy by pressure overload in the present study.

In conclusion, dystrophin-deficient myocardium is vulnerable to pressure overload in vivo. This result has two clinical implications: (1) the patients with dystrophynopathy, such as DMD, BMD and X-linked type of dilated cardiomyopathy, who develop arterial hypertension should be treated aggressively, and (2) they should avoid stresses that elevate blood pressure.

Time for primary review 26 days.


   Acknowledgements
 
This study was presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, FL, 1997 and supported in part by the Scientific Research Grant from the Ministry of Education, Science and Culture of Japan.


   References
Top
 Abstract
 1 Introduction
 2 Methods
 3 Results
 4 Discussion
 References
 

  1. Hoffman E.P., Brown R.H. Jr., Kunkel L.M. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell (1987) 51:919–928.[CrossRef][Web of Science][Medline]
  2. Koenig M., Hoffman E.P., Bertelson C.J., Monaco A.P., Feener C., Kunkel L.M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell (1987) 50:509–517.[CrossRef][Web of Science][Medline]
  3. Koenig M., Monaco A.P., Kunkel L.M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell (1988) 53:219–226.[CrossRef][Web of Science][Medline]
  4. Campbell K.P., Kahl S.D. Association of dystrophin and an integral membrane glycoprotein. Nature (1989) 338:259–262.[CrossRef][Medline]
  5. Arahata K., Ishiura S., Ishiguro T., et al. Immunostaining of skeletal and cardiac muscle surface membrane with antibody against Duchenne muscular dystrophy peptide. Nature (1988) 333:861–863.[CrossRef][Medline]
  6. Monaco A.P., Neve R.L., Colletti-Feener C., Bertelson C.J., Kurnit D.M., Kunkel L.M. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature (1986) 323:646–650.[CrossRef][Medline]
  7. Burghes A.H., Logan C., Hu X., Belfall B., Worton R.G., Ray P.N. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. Nature (1987) 328:434–437.[CrossRef][Medline]
  8. Towbin J.A., Hejtmancik J.F., Brink P., et al. X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Circulation (1993) 87:1854–1865.[Abstract/Free Full Text]
  9. Hemmings L., Kuhlman P.A., Critchley D.R. Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain. J Cell Biol (1992) 116:1369–1380.[Abstract/Free Full Text]
  10. Henry M.D., Campbell K.P. Dystroglycan: an extracellular matrix receptor linked to the cytoskeleton. Curr Opin Cell Biol (1996) 8:625–631.[CrossRef][Web of Science][Medline]
  11. Ervasti J.M., Campbell K.P. A role for the dystrophin–glycoprotein complex as a transmembrane linker between laminin and actin. J Cell Biol (1993) 122:809–823.[Abstract/Free Full Text]
  12. Ervasti J.M., Ohlendieck K., Kahl S.D., Gaver M.G., Campbell K.P. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature (1990) 345:315–319.[CrossRef][Medline]
  13. Yoshida M., Ozawa E. Glycoprotein complex anchoring dystrophin to sarcolemma. J Biochem (1990) 108:748–752.[Abstract/Free Full Text]
  14. Suzuki A., Yoshida M., Yamamoto H., Ozawa E. Glycoprotein-binding site of dystrophin is confined to the cysteine-rich domain and the first half of the carboxy-terminal domain. FEBS Lett (1992) 308:154–160.[CrossRef][Web of Science][Medline]
  15. Ibraghimov-Beskrovnaya O., Ervasti J.M., Leveille C.J., Slaughter C.A., Sernett S.W., Campbell K.P. Primary structure of dystrophin-associated glycoproteins linking dystrophin to the extracellular matrix. Nature (1992) 355:696–702.[CrossRef][Medline]
  16. Suzuki A., Yoshida M., Hayashi K., Mizuno Y., Hagiwara Y., Ozawa E. Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin. Eur J Biochem (1994) 220:283–292.[Web of Science][Medline]
  17. Crosbie R.H., Heighway J., Venzke D.P., Lee J.C., Campbell K.P. Sarcospan, the 25-kDa transmembrane component of the dystrophin–glycoprotein complex. J Biol Chem (1997) 272:31221–31224.[Abstract/Free Full Text]
  18. Blake D.J., Nawrotzki M.F., Peters S.C., Froehner S.C., Davies K.E. Isoform diversity of dystrobrevin, the murine 87-kDa postsynaptic protein. J Biol Chem (1996) 271:7802–7810.[Abstract/Free Full Text]
  19. Sadoulet-Puccio H.M., Khurana T.S., Cohen J.B., Kunkel L.M. Cloning and characterization of the human homologue of a dystrophin related phosphoprotein found at the Torpedo electric organ post-synaptic membrane. Hum Mol Genet (1996) 5:489–496.[Abstract/Free Full Text]
  20. Olson T.M., Michels V.V., Thibodeau S.N., Tai Y.S., Keating M.T. Actin mutations in dilated cardiomyopathy, a heritable form of heart failure. Science (1998) 280:750–752.[Abstract/Free Full Text]
  21. Helbling-Leclerc A., Zhang X., Topaloglu H., et al. Mutations in the laminin alpha 2-chain gene (LAMA2) cause merosin-deficient congenital muscular dystrophy. Nat Genet (1995) 11:216–218.[CrossRef][Web of Science][Medline]
  22. Worton R. Muscular dystrophies: diseases of the dystrophin–glycoprotein complex. Science (1995) 270:755–756.[Abstract/Free Full Text]
  23. Campbell K.P. Three muscular dystrophies: loss of cytoskeleton–extracellular matrix linkage. Cell (1995) 80:675–679.[CrossRef][Web of Science][Medline]
  24. Straub V., Campbell K.P. Muscular dystrophies and the dystrophin–glycoprotein complex. Curr Opin Neurol (1997) 10:168–175.[Web of Science][Medline]
  25. Towbin J.A. The role of cytoskeletal proteins in cardiomyopathies. Curr Opin Cell Biol (1998) 10:131–139.[CrossRef][Web of Science][Medline]
  26. Mayer U., Saher G., Fassler R., et al. Absence of integrin alpha 7 causes a novel form of muscular dystrophy. Nat Genet (1997) 17:318–323.[Web of Science][Medline]
  27. Petrof B.J., Shrager J.B., Stedman H.H., Kelly A.M., Sweeney H.L. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA (1993) 90:3710–3714.[Abstract/Free Full Text]
  28. Moens P., Baatsen P.H., Marechal G. Increased susceptibility of EDL muscles from mdx mice to damage induced by contractions with stretch. J Muscle Res Cell Motil (1993) 14:446–451.[CrossRef][Web of Science][Medline]
  29. Menke A., Jockusch H. Decreased osmotic stability of dystrophin-less muscle cells from the mdx mouse. Nature (1991) 349:69–71.[CrossRef][Medline]
  30. Menke A., Jockusch H. Extent of shock-induced membrane leakage in human and mouse myotubes depends on dystrophin. J Cell Sci (1995) 108:727–733.[Abstract]
  31. Rockman H.A., Ross R.S., Harris A.N., et al. Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA (1991) 88:8277–8281.[Abstract/Free Full Text]
  32. Kojima M., Shiojima I., Yamazaki T., et al. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Circulation (1994) 89:2204–2211.[Abstract/Free Full Text]
  33. Carter G.T., Wineinger M.A., Walsh S.A., Horasek S.J., Abresch R.T., Fowler W.M. Jr. Effect of voluntary wheel-running exercise on muscles of the mdx mouse. Neuromuscul Disord (1995) 5:323–332.[CrossRef][Web of Science][Medline]
  34. Vilquin J.T., Brussee V., Asselin I., Kinoshita I., Gingras M., Tremblay J.P. Evidence of mdx mouse skeletal muscle fragility in vivo by eccentric running exercise. Muscle Nerve (1998) 21:567–576.[CrossRef][Web of Science][Medline]
  35. Rando T.A., Disatnik M.H., Yu Y., Franco A. Muscle cells from mdx mice have an increased susceptibility to oxidative stress. Neuromuscul Disord (1998) 8:14–21.[CrossRef][Web of Science][Medline]
  36. Rafael J., Gorospe M., Tharp M., Demitsu T., Hoffman E.-P. Dystrophin-deficient myofibers are vulnerable to mast cell granule-induced necrosis. Neuromuscul Disord (1994) 4:325–333.[CrossRef][Web of Science][Medline]
  37. Anderson J.E., Liu L., Kardami E. The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater dystrophy in cardiac and soleus muscle. Muscle Nerve (1994) 17:64–73.[CrossRef][Web of Science][Medline]
  38. Turner P.R., Westwood T., Regen C.M., Steinhardt R.A. Increased protein degradation results from elevated free calcium levels found in muscle from mdx mice. Nature (1988) 335:735–738.[CrossRef][Medline]
  39. Fong P.Y., Turner P.R., Denetclaw W.F., Steinhardt R.A. Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin. Science (1990) 250:673–676.[Abstract/Free Full Text]
  40. Franco A. Jr., Lansman J.B. Calcium entry through stretch-inactivated ion channels in mdx myotubes. Nature (1990) 344:670–673.[CrossRef][Medline]
  41. Gottlieb R.A., Burleson K.O., Kloner R.A., et al. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest (1994) 94:1621–1628.[Web of Science][Medline]
  42. Feuerstein G.Z., Young P.R. Apoptosis in cardiac disease: stress- and mitogen-activated signaling pathways. Cardiovasc Res (2000) 45:560–569.[Abstract/Free Full Text]
  43. Teiger E., Than V.D., Richard L., et al. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J Clin Invest (1996) 97:2891–2897.[Web of Science][Medline]
  44. Tidball J.G., Albrecht D.E., Lokensgard B.E., Spencer M.J. Apoptosis precedes necrosis of dystrophin-deficient muscle. J Cell Sci (1995) 108:2197–2204.[Abstract]
  45. Hirakawa T., Maeda M., Setoguchi M., Kamogawa Y., Biro S. Mechanical stretch induces apoptosis in dystrophin-deficient cultured cardiac myocytes [abstract]. Circulation (1999) 100:282.
  46. Coral-Vazquez R., Cohn R.D., Moore S.A., et al. Disruption of the sarcoglycan sarcospan in vascular smooth muscle: a novel mechanism for cardiomyopathy and muscular dystrophy. Cell (1999) 98:465–474.[CrossRef][Web of Science][Medline]
  47. Gnecchi-Ruscone T., Taylor J., Mercuri E., et al. Cardiomyopathy in Duchenne, Becker, and sarcoglycanopathies: a role for coronary dysfunction? Muscle Nerve (1999) 22:1549–1556.[CrossRef][Web of Science][Medline]
  48. Sicinski P., Geng Y., Ryder-Cook A.S., Barnard E.A., Darlison M.G., Barnard P.J. The molecular basis of muscular dystrophy in the mdx mouse: a point mutation. Science (1989) 244:1578–1580.[Abstract/Free Full Text]
  49. Pastoret C., Sebille A. mdx mice show progressive weakness and muscle deterioration with age. J Neurol Sci (1995) 129:97–105.[CrossRef][Web of Science][Medline]
  50. Pons F., Robert A., Fabbrizio E., et al. Utrophin localization in normal and dystrophin-deficient heart. Circulation (1994) 90:369–374.[Abstract/Free Full Text]
  51. Grady R.M., Teng H., Nichol M.C., Cunningham J.C., Wilkinson R.S., Sanes J.R. Skeletal and cardiac myopathies in mice lacking utrophin and dystrophin: a model for Duchenne muscular dystrophy. Cell (1997) 90:729–738.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J Heart FailHome page
R. Bauer, V. Straub, A. Blain, K. Bushby, and G. A. MacGowan
Contrasting effects of steroids and angiotensin-converting-enzyme inhibitors in a mouse model of dystrophin-deficient cardiomyopathy
Eur J Heart Fail, May 1, 2009; 11(5): 463 - 471.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
L. Elsherif, M. S. Huang, S.-Y. Shai, Y. Yang, R. Y. Li, J. Chun, M. A. Mekany, A. L. Chu, S. J. Kaufman, and R. S. Ross
Combined Deficiency of Dystrophin and {beta}1 Integrin in the Cardiac Myocyte Causes Myocardial Dysfunction, Fibrosis and Calcification
Circ. Res., May 9, 2008; 102(9): 1109 - 1117.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kamogawa, Y.
Right arrow Articles by Tei, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kamogawa, Y.
Right arrow Articles by Tei, C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?