Limits...
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.

Show MeSH

Related in: MedlinePlus

Heart’s specimen from a control mouse. The measuring frame of 70×50 μm is marked. In the black frame – vessel. Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3539494&req=5

f1-medscimonit-17-11-br332: Heart’s specimen from a control mouse. The measuring frame of 70×50 μm is marked. In the black frame – vessel. Scale bar = 50 μm.

Mentions: Five samples from each group were chosen for analysis, and 6 preparations from each mouse were examined. Five fields of myocardium measuring 70×50 μm and not containing blood vessels were evaluated in each preparation (Figure 1). The result recorded for each mouse was the mean of the values obtained for each sample. Endothelial specimens on similar field sizes that contained cardiac vessels only were evaluated, and the mean value of all results was calculated for every group of 5 mice.


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)

Heart’s specimen from a control mouse. The measuring frame of 70×50 μm is marked. In the black frame – vessel. Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

f1-medscimonit-17-11-br332: Heart’s specimen from a control mouse. The measuring frame of 70×50 μm is marked. In the black frame – vessel. Scale bar = 50 μm.
Mentions: Five samples from each group were chosen for analysis, and 6 preparations from each mouse were examined. Five fields of myocardium measuring 70×50 μm and not containing blood vessels were evaluated in each preparation (Figure 1). The result recorded for each mouse was the mean of the values obtained for each sample. Endothelial specimens on similar field sizes that contained cardiac vessels only were evaluated, and the mean value of all results was calculated for every group of 5 mice.

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