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Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor.

Nowak D, Kozlowska H, Gielecki JS, Rowinski J, Zurada A, Goralczyk K, Bozilow W - Med. Sci. Monit. (2011)

Bottom Line: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue.In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent.Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland. dareknowak15@wp.pl

ABSTRACT

Background: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A.

Material/methods: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization.

Results: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent.

Conclusions: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy.

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Related in: MedlinePlus

In situ hybridization analysis of VEGF mRNA expression in cardiac vessel endothelial cells (A) and in cardiac myocytes (B) from normal (C57BI/10ScSn) and mdx (C57BI/10ScSn) mice (values are optical densities expressed as percentage of the signal for control mice). N – 5 samples from each group, 5 fields of myocardium in 6 preparations from each mouse were examined together 150 analysis. * Statistically significant compared to normal – healthy mice.
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f3-medscimonit-17-11-br332: In situ hybridization analysis of VEGF mRNA expression in cardiac vessel endothelial cells (A) and in cardiac myocytes (B) from normal (C57BI/10ScSn) and mdx (C57BI/10ScSn) mice (values are optical densities expressed as percentage of the signal for control mice). N – 5 samples from each group, 5 fields of myocardium in 6 preparations from each mouse were examined together 150 analysis. * Statistically significant compared to normal – healthy mice.

Mentions: Effects on VEGF mRNA expression are depicted in Figure 3A for the cardiac vessel endothelium cells and in Figure 3B for the myocardium. In the case of cardiac endothelium cells, there was no difference in VEGF-A mRNA expression between the control groups for normal and mdx mice (101±8% vs. 99±7%, respectively) (p>0.05) or between the normal and dystrophic mice immediately following exposure to hypoxia (103±9% vs. 98±8%, respectively) (p>0.05), on day 1 (228±13% vs. 233±14%) (p>0.05), and on day 3 (144±10% vs. 133±8%) (p>0.05). However, on day 1 there was a marked increase in VEGF-A mRNA expression in normal and mdx mice exposed to hypoxia as compared to normobaric control mice. By day 7, VEGF-A mRNA expression levels had returned to their initial levels (106±10% vs. 93±13%, respectively) (p>0.05).


Cardiomyopathy in the mouse model of Duchenne muscular dystrophy caused by disordered secretion of vascular endothelial growth factor.

Nowak D, Kozlowska H, Gielecki JS, Rowinski J, Zurada A, Goralczyk K, Bozilow W - Med. Sci. Monit. (2011)

In situ hybridization analysis of VEGF mRNA expression in cardiac vessel endothelial cells (A) and in cardiac myocytes (B) from normal (C57BI/10ScSn) and mdx (C57BI/10ScSn) mice (values are optical densities expressed as percentage of the signal for control mice). N – 5 samples from each group, 5 fields of myocardium in 6 preparations from each mouse were examined together 150 analysis. * Statistically significant compared to normal – healthy mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539494&req=5

f3-medscimonit-17-11-br332: In situ hybridization analysis of VEGF mRNA expression in cardiac vessel endothelial cells (A) and in cardiac myocytes (B) from normal (C57BI/10ScSn) and mdx (C57BI/10ScSn) mice (values are optical densities expressed as percentage of the signal for control mice). N – 5 samples from each group, 5 fields of myocardium in 6 preparations from each mouse were examined together 150 analysis. * Statistically significant compared to normal – healthy mice.
Mentions: Effects on VEGF mRNA expression are depicted in Figure 3A for the cardiac vessel endothelium cells and in Figure 3B for the myocardium. In the case of cardiac endothelium cells, there was no difference in VEGF-A mRNA expression between the control groups for normal and mdx mice (101±8% vs. 99±7%, respectively) (p>0.05) or between the normal and dystrophic mice immediately following exposure to hypoxia (103±9% vs. 98±8%, respectively) (p>0.05), on day 1 (228±13% vs. 233±14%) (p>0.05), and on day 3 (144±10% vs. 133±8%) (p>0.05). However, on day 1 there was a marked increase in VEGF-A mRNA expression in normal and mdx mice exposed to hypoxia as compared to normobaric control mice. By day 7, VEGF-A mRNA expression levels had returned to their initial levels (106±10% vs. 93±13%, respectively) (p>0.05).

Bottom Line: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue.In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent.Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart.

View Article: PubMed Central - PubMed

Affiliation: Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Torun, Poland. dareknowak15@wp.pl

ABSTRACT

Background: Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that affects skeletal muscles and cardiac muscle tissue. In some cases, myocardial injury secondary to hypoxia can lead to dilative cardiomyopathy (DCM). A genetic defect in the dystrophin gene may increase the susceptibility of myocardium to hypoxia. Available data suggest that this may be caused by impaired secretion of NO, which is bound with secretion of VEGF-A.

Material/methods: Male mice C57BI/10ScSn mdx (animal model of DMD) and healthy mice C57BI/10ScSn were exposed to hypobaric hypoxia in low-pressure chambers. Their hearts were harvested immediately after and 1, 3, 7, and 21 days after exposure to hypoxia. Normobaric mice were used as controls. The expression of VEGF-A in myocardium and cardiac vessel walls was evaluated using immunohistochemistry, Western blotting, and in situ hybridization.

Results: VEGF-A expression in myocardium and vessel walls of healthy mice peaked 24 hours after exposure to hypoxia. The expression of VEGF-A in vessel walls was similar in dystrophic and healthy mice; however, VEGF-A expression in the myocardium of dystrophic mice was impaired, peaking around day 7. In the heart, the total level of VEGF depends on VEGF expression in myocardium, not in vessel endothelium, and our research demonstrates that the expression of VEGF is dystrophin-dependent.

Conclusions: Disordered secretion of VEGF-A in hypoxic myocardium caused the total level of this factor to be impaired in the heart. This factor, which in normal situations protect against hypoxia, promotes the gradual progression of cardiomyopathy.

Show MeSH
Related in: MedlinePlus