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Regular exercise or changing diet does not influence aortic valve disease progression in LDLR deficient mice.

Schlotter F, Matsumoto Y, Mangner N, Schuler G, Linke A, Adams V - PLoS ONE (2012)

Bottom Line: Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0).Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers.Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD.

View Article: PubMed Central - PubMed

Affiliation: University of Leipzig-Heart Center Leipzig, Department of Internal Medicine/Cardiology, Leipzig, Germany.

ABSTRACT

Background: The development and progression of calcific aortic valve disease (CAVD) shares a number of similarities with atherosclerosis. Recently we could demonstrate that regular exercise training (ET) as primary prevention prevents aortic valve disease in LDL-receptor deficient (LDLR(-/-)) mice. We aimed to investigate the impact of exercise training on the progression of CAVD in LDLR(-/-) mice in the setting of secondary prevention

Methods and results: Sixty-four LDLR(-/-) mice were fed with high cholesterol diet to induce aortic valve sclerosis. Thereafter the animals were divided into 3 groups: group 1 continuing on high cholesterol diet, group 2 continuing with cholesterol diet plus 1 h ET per day, group 3 continuing with normal mouse chow. After another 16 weeks the animal were sacrificed. Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0). Immunohistochemical staining for endothelial cells revealed a disrupted endothelial cell layer to the same extend in all groups. Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers.

Conclusion: Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD.

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Related in: MedlinePlus

Representative immunostainings for macrophages (Mac3), vascular smooth muscle cells and valvular myofibroblast-like cells (α-smooth muscle actin [α-SMA]), and a phenotypic marker of osteoblast differentiation (osteopontin [OPN]) (A).Semi-quantitative analysis of infiltration of macrophages (B), valvular myofibroblast-like cells (C), and osteoblast-type cells (D) in 9 animals from each group. Arrowheads demonstrate areas of positive immunostaining at the vascular smooth muscle cell layer (α-SMA) and the atherosclerotic areas of the aortic sinus (Mac3). Bar = 100 µm.
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pone-0037298-g004: Representative immunostainings for macrophages (Mac3), vascular smooth muscle cells and valvular myofibroblast-like cells (α-smooth muscle actin [α-SMA]), and a phenotypic marker of osteoblast differentiation (osteopontin [OPN]) (A).Semi-quantitative analysis of infiltration of macrophages (B), valvular myofibroblast-like cells (C), and osteoblast-type cells (D) in 9 animals from each group. Arrowheads demonstrate areas of positive immunostaining at the vascular smooth muscle cell layer (α-SMA) and the atherosclerotic areas of the aortic sinus (Mac3). Bar = 100 µm.

Mentions: Immunostaining for Mac-3, a marker for the presence of macrophages, was performed. Semi-quantitative analysis revealed a high level of macrophage infiltration of the AV leaflets that was almost identical among the three groups (Figure 4). Oxidative stress levels were assessed by in-situ Dihydroethidium (DHE) fluorescence. No significant difference in the degree of superoxide expression was observed between the groups (data not shown). Therefore, exercise training or a change in diet had no significant impact on the inflammatory process or the load with reactive oxygen species inside the AVs.


Regular exercise or changing diet does not influence aortic valve disease progression in LDLR deficient mice.

Schlotter F, Matsumoto Y, Mangner N, Schuler G, Linke A, Adams V - PLoS ONE (2012)

Representative immunostainings for macrophages (Mac3), vascular smooth muscle cells and valvular myofibroblast-like cells (α-smooth muscle actin [α-SMA]), and a phenotypic marker of osteoblast differentiation (osteopontin [OPN]) (A).Semi-quantitative analysis of infiltration of macrophages (B), valvular myofibroblast-like cells (C), and osteoblast-type cells (D) in 9 animals from each group. Arrowheads demonstrate areas of positive immunostaining at the vascular smooth muscle cell layer (α-SMA) and the atherosclerotic areas of the aortic sinus (Mac3). Bar = 100 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351435&req=5

pone-0037298-g004: Representative immunostainings for macrophages (Mac3), vascular smooth muscle cells and valvular myofibroblast-like cells (α-smooth muscle actin [α-SMA]), and a phenotypic marker of osteoblast differentiation (osteopontin [OPN]) (A).Semi-quantitative analysis of infiltration of macrophages (B), valvular myofibroblast-like cells (C), and osteoblast-type cells (D) in 9 animals from each group. Arrowheads demonstrate areas of positive immunostaining at the vascular smooth muscle cell layer (α-SMA) and the atherosclerotic areas of the aortic sinus (Mac3). Bar = 100 µm.
Mentions: Immunostaining for Mac-3, a marker for the presence of macrophages, was performed. Semi-quantitative analysis revealed a high level of macrophage infiltration of the AV leaflets that was almost identical among the three groups (Figure 4). Oxidative stress levels were assessed by in-situ Dihydroethidium (DHE) fluorescence. No significant difference in the degree of superoxide expression was observed between the groups (data not shown). Therefore, exercise training or a change in diet had no significant impact on the inflammatory process or the load with reactive oxygen species inside the AVs.

Bottom Line: Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0).Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers.Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD.

View Article: PubMed Central - PubMed

Affiliation: University of Leipzig-Heart Center Leipzig, Department of Internal Medicine/Cardiology, Leipzig, Germany.

ABSTRACT

Background: The development and progression of calcific aortic valve disease (CAVD) shares a number of similarities with atherosclerosis. Recently we could demonstrate that regular exercise training (ET) as primary prevention prevents aortic valve disease in LDL-receptor deficient (LDLR(-/-)) mice. We aimed to investigate the impact of exercise training on the progression of CAVD in LDLR(-/-) mice in the setting of secondary prevention

Methods and results: Sixty-four LDLR(-/-) mice were fed with high cholesterol diet to induce aortic valve sclerosis. Thereafter the animals were divided into 3 groups: group 1 continuing on high cholesterol diet, group 2 continuing with cholesterol diet plus 1 h ET per day, group 3 continuing with normal mouse chow. After another 16 weeks the animal were sacrificed. Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0). Immunohistochemical staining for endothelial cells revealed a disrupted endothelial cell layer to the same extend in all groups. Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers.

Conclusion: Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD.

Show MeSH
Related in: MedlinePlus